Publications by authors named "Xuegang Wang"

36 Publications

Lysophosphatidylcholine induces apoptosis and inflammatory damage in brain microvascular endothelial cells via GPR4-mediated NLRP3 inflammasome activation.

Toxicol In Vitro 2021 Jul 20;77:105227. Epub 2021 Jul 20.

Department of Neurology, University of Chinese Academy of Sciences Shenzhen Hospital (Guang ming), No. 39 Huaxia Road, Guangming District, Shenzhen 518107, China. Electronic address:

Lysophosphatidylcholine (LPC), as the main active component of oxidized low-density lipoproteins (ox-LDLs), has significant effects in cerebrovascular disease. However, the complex mechanism by which LPC functions in brain microvascular endothelial cells (BMECs) is not clearly understood. In this study, BMECs were transfected with G protein-coupled receptor 4 (GPR4) siRNA or an NLRP3-overexpression plasmid, and GPR4 expression was identified by RT-qPCR and western blotting; IL-1β, IL-18, and IL-33 levels were evaluated by ELISA. Apoptosis was monitored by flow cytometry and Hoechst staining, while Caspase 3, ASC, NLRP3, and GPR4 protein expression were examined by western blotting. Our results showed that LPC significantly increased the levels of inflammatory cytokines (IL-1β, IL-18, and IL-33) and markedly induced apoptosis and NLRP3 inflammasome activation in BMECs. Moreover, LPC notably upregulated GPR4 in BMECs, and knockdown of GPR4 significantly attenuated the effects of LPC in BMECs. Above all, we also proved that LPC induced apoptosis and inflammatory injury in BMECs by causing GPR4 to activate NLRP3 inflammasomes. Therefore, GPR4-mediated activation of NLRP3 inflammasomes might be the underlying mechanism by which LPC promotes the progression of cerebrovascular disease. In summary we found that LPC is an important pathogenic factor in cerebrovascular disease, and can induce GPR4 to active NLRP3 inflammasomes.
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http://dx.doi.org/10.1016/j.tiv.2021.105227DOI Listing
July 2021

Identification of HIPK3 as a potential biomarker and an inhibitor of clear cell renal cell carcinoma.

Aging (Albany NY) 2021 01 20;13(3):3536-3553. Epub 2021 Jan 20.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Invasion and metastasis are the main causes of poor prognosis in patients with clear cell renal cell carcinoma (ccRCC). The homeodomain interacting protein kinases (HIPKs) can regulate cell proliferation and apoptosis. Little is known about the prognostic role of HIPKs in ccRCC. Here we use Kaplan-Meier survival analysis and multivariate analysis to analyze the correlation of overall survival (OS) and disease-free survival (DFS). ROC curves analyzed the relationship between clinicopathological parameters and HIPK3 expression in ccRCC. Univariate analysis and multivariate analysis confirmed that the expression of HIPK3 was associated with OS (HR, 0.701; P=0.041) and DFS (HR, 0.630; P=0.012). Low HIPK3 expression was a poor prognostic factor and HIPK3 expression was significantly down-regulated in ccRCC cancer tissues when compared with normal renal tissues. cell results also confirmed that HIPK3 over-expression could inhibit tumor growth and malignant characteristics. The results indicate that low expression of HIPK3 in ccRCC tissues is significantly associated with poor survival rates in tumor patients, and HIPK3 may be used as a valuable biomarker and inhibitor of ccRCC.
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http://dx.doi.org/10.18632/aging.202294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906163PMC
January 2021

Identification of potential therapeutic targets in urothelial bladder carcinoma of Chinese population by targeted next-generation sequencing.

Cancer Biol Ther 2020 08 23;21(8):709-716. Epub 2020 May 23.

The Key Laboratory of Urinary Tract Tumors and Calculi, Department of Urology Surgery, The First Affiliated Hospital, School of Medicine, Xiamen University , Xiamen, China.

Patients with urothelial carcinoma (UC) of the bladder have a high risk of death in China. However, a lack of comprehensive molecular profiling in Chinese Han population hinders the development of targeted therapies for bladder cancer. In our present study, we collected fresh bladder tumors from low-grade (T1, N0, M0, G1) non-muscle invasive bladder cancer (NMIBC) patients (n = 16) and high-grade (T2-4, N0, M0, Gx) muscle-invasive bladder cancer (MIBC) patients (n = 16) with their paired normal bladder tissues, and subjected the total genomic DNAs to targeted next-generation sequencing (NGS) for 94 cancer-associated genes. NGS results showed that 30.9% of detected genes (29/94) was mutated in 32 urothelial carcinoma bladder tissues. Furthermore, our results and ICGC database showed that , and were the most frequently mutated genes in UC patients. Of note, NMIBC and MIBC displayed distinguishable genomic alterations. , and were the most frequently mutated genes in NMIBC patients, whereas mutations of , and were frequently detected in MIBC. Intriguingly, gene ontology and clustering analysis revealed that these frequently mutated genes were highly enriched in signaling pathways responsible for cancer development. Taken together, the mutation frequency of genes associated with UC development in NMIBC and MIBC was screened out in Chinese Han population and elucidation of the related mechanisms provides theoretical basis and technical support for the development of early diagnosis and therapeutic strategies in UC.
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http://dx.doi.org/10.1080/15384047.2020.1763148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515499PMC
August 2020

Photocatalytic decontamination of tetracycline and Cr(VI) by a novel α-FeOOH/FeS photocatalyst: One-pot hydrothermal synthesis and Z-scheme reaction mechanism insight.

J Hazard Mater 2020 10 26;397:122580. Epub 2020 Apr 26.

State Key Laboratory of Nuclear Resources and Environment, East China University of Technology, Nanchang, 330013, China; School of Water Resources & Environmental Engineering, East China University of Technology, Nanchang, 330013, China. Electronic address:

Tetracycline and Cr(VI) as non-biodegradable environmental contaminants have attracted increasing attention because of their chronic toxicity. In this regard, the environmentally friendly Z-scheme photocatalytic decontamination system has been widely used for contaminant treatment. Herein, a novel 3D Z-scheme α-FeOOH/FeS composite photocatalyst was successfully synthesized for the first time via a simple one-pot hydrothermal method. X-ray diffraction (XRD) and Fourier-transform infrared (FT-IR) analyses and high-resolution transmission electron microscopy (HRTEM) and X-ray photoelectron spectroscopy (XPS) demonstrated that the O component of the heterogeneous nanostructures formed by the FeOFe linkages in α-FeOOH was replaced by S to generate FeSFe linkages in the resulting FeS. As expected, the novel 3D Z-scheme α-FeOOH/FeS composites exhibited remarkable photocatalytic activity for Cr(VI) reduction and tetracycline degradation compared to pure α-FeOOH. Photoluminesence (PL) measurement and electrochemical impedance spectroscopy (EIS), as well as density functional theory (DFT) calculations, suggested that the enhanced photocatalytic activity of the Z-scheme α-FeOOH/FeS composite can be attributed to the improved photo-absorption properties and the effective separation of photo-induced charge carriers caused by the Z-scheme system of the as-prepared 3D α-FeOOH/FeS composites. Thus, this work may facilitate the effective design of α-FeOOH-based photocatalysts.
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http://dx.doi.org/10.1016/j.jhazmat.2020.122580DOI Listing
October 2020

miR-489-3p Inhibits Prostate Cancer Progression by Targeting DLX1.

Cancer Manag Res 2020 23;12:2719-2729. Epub 2020 Apr 23.

The Key Laboratory of Urinary Tract Tumors and Calculi, Department of Urology Surgery, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen 361003, People's Republic of China.

Purpose: Prostate cancer (PCa) is the third most common cancer in men and the second leading cause of cancer-related death in men. DLX1 belongs to the DLX homeobox family and exhibits antitumor activity in many kinds of tumors. MicroRNAs (miRNAs) play important roles in the progression of cancer. However, whether miRNAs affect the development of PCa by targeting DLX1 has not been determined. In this study, we aimed to investigate the role of miR-489-3p in the regulation of DLX1 expression and PCa progression and to provide a potential therapeutic target for PCa treatment.

Methods and Materials: The Cancer Genome Atlas database was used to analyze the divergent expression of DLX1 in carcinomas and adjacent normal tissues. The expression level of DLX1 in malignant and normal prostate cells was also measured using RT-qPCR and Western blotting. A dual-luciferase reporter assay was performed to determine whether miR-489-3p directly targets DLX1. We transfected 22Rv1 and DU145 cells with miR-489-3p mimics to overexpress miR-489-3p and then evaluated its effect on cellular function. MTT, EdU, colony formation and cell cycle assays were used to evaluate cell growth. JC-1 and ROS assays with flow cytometry were performed to indirectly analyze apoptosis. Transwell assays were conducted to investigate metastasis.

Results: The expression level of DLX1 was upregulated in both PCa tissues and cell lines. MiR-489-3p directly targeted DLX1 and downregulated its expression. Overexpression of miR-489-3p significantly suppressed cell growth. MiR-489-3p induced apoptosis through mitochondrial function impairment. Overexpression of miR-489-3p also inhibited cell migration and invasion. DLX1 overexpression reversed the above effects induced by miR-489-3p.

Conclusion: We identified the involvement of the miR-489-3p/DLX1 pathway in PCa for the first time. In this pathway, miR-489-3p acts as a tumor suppressor by negatively regulating the expression of DLX1. MiR-489-3p may be a potential therapeutic target for PCa treatment.
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http://dx.doi.org/10.2147/CMAR.S239796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185642PMC
April 2020

Retrograde en bloc resection for non-muscle invasive bladder tumor can reduce the risk of seeding cancer cells into the peripheral circulation.

World J Surg Oncol 2020 Feb 10;18(1):33. Epub 2020 Feb 10.

Department of Urology, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Siming District, Xiamen, 361003, Fujian, China.

Objective: To ascertain whether en bloc resection could reduce the risk of seeding cancer cells into the circulation during the resection of non-muscle invasive bladder cancer (NMIBC).

Methods: Patients with primary NMIBC were enrolled in this prospective study from October 2017 to May 2018. Patients were allocated to receive conventional transurethral resection of the bladder (TURB) or retrograde en bloc resection technique of the bladder tumor (RERBT). Blood samples (1 ml) for circulating tumor cell (CTC) enumeration were drawn from the peripheral vein prior to resection (PV1), immediately after resection of the tumor base (PV2), and at 12 h after resection (PV3). Intra-group comparisons of the changes in the number of CTCs identified among the PV1, PV2, and PV3 blood samples were performed in each group.

Results: A total of 21 patients (12 in the RERBT group and 9 in the TURB group) were recruited. For patients receiving TURB, the level of CTCs identified in PV3 was significantly higher than that in PV1 (p = 0.047). However, there was no significant difference in CTC counts before and after resection in the RERBT group.

Conclusion: RERBT did not increase the number of tumor cells in the bloodstream.
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http://dx.doi.org/10.1186/s12957-020-1808-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011233PMC
February 2020

MiR-765 functions as a tumour suppressor and eliminates lipids in clear cell renal cell carcinoma by downregulating PLP2.

EBioMedicine 2020 Jan 3;51:102622. Epub 2020 Jan 3.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. Electronic address:

Background: Lipid accumulation has been highlighted in cancer development and progression, but the exact mechanism remains unclear in renal cell carcinoma (RCC). MicroRNAs (miRNAs) have been confirmed to participate in the pathological processes of cancers, including tumour occurrence and inhibition. However, the role and mechanism of miR-765 have not been elucidated in clear cell renal cell carcinoma (ccRCC).

Methods: Using The Cancer Genome Atlas (TCGA) database and qRT-PCR, we investigated differences in miR-765 and proteolipid protein 2 (PLP2) expression, as well as their clinical relevance. To investigate the function of miR-765 and PLP2 in ccRCC, we performed in vitro and in vivo experiments to explore their biological functions in ccRCC.

Findings: In this study, we showed that miR-765 was upregulated in the plasma of ccRCC patients after tumour resection. Consistently, ccRCC tissues had low expression of miR-765 when compared with corresponding non-cancerous tissues. Overexpression of miR-765 suppressed cell proliferation and metastasis in vitro and in vivo. Mechanistic studies demonstrated that PLP2 was a direct target gene of miR-765. PLP2 was highly expressed in ccRCC tissues, and high PLP2 levels were positively correlated with higher tumour stage and grade and poor prognosis. PLP2 expression was negatively correlated with the miR-765 level in patient samples. We further showed that PLP2 restrained the cell metastasis and proliferation induced by miR-765 and reduced the lipid-eliminating effects of miR-765 in renal cancer cells.

Interpretation: Our findings suggest that miR-765 may function as a tumour suppressor and eliminate lipids in clear cell renal cell carcinoma by targeting PLP2.

Funding: This work was funded the grants from the National Natural Scientific Foundation of China (Grant No. 81672528, 81672524, 81602218, 31741032, 81902588).
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http://dx.doi.org/10.1016/j.ebiom.2019.102622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6948168PMC
January 2020

Circular RNA ITCH suppressed prostate cancer progression by increasing HOXB13 expression via spongy miR-17-5p.

Cancer Cell Int 2019 3;19:328. Epub 2019 Dec 3.

1Department of Urology, The First Affiliated Hospital of Xiamen University, The First Clinical College of Fujian Medical University, Xiamen, 361003 Fujian People's Republic of China.

Background: Circular RNA Itchy E3 ubiquitin protein ligase (Circ-ITCH) is significantly down-regulated in various kinds of tumors, however, the mechanisms of action and functions of circITCH gene in prostate cancer (PC) are still under investigation. The mail goal of this research was to study the functional role of Circ-ITCH gene in prostate cancer and to illuminate the function role of circ-ITCH gene in prostate cancer by targeting miR-17-5p/HOXB13.

Methods: RT-qPCR was applied to measure the expression level of circ-ITCH and miR-17-5p in PC cell lines and tissues. CCK-8, colony formation, Brdu incorporation labeling and flow cytometry assays were applied to detect the effects of circ-ITCH and miR-17-5p on proliferation and cell apoptosis. Target gene prediction and screening, luciferase reporter gene assays were utilized to assess downstream target genes of miR-17-5p and Circ-ITCH. The protein and expression of HOXB13 gene were measured by Western blotting and RT-qPCR.

Results: CircITCH was significantly reduced in PC cell lines and tissues. Low circITCH expression level was highly related with preoperative PSA, tumor stage and Gleason score. Overexpression of circITCH can inhibit the malignant phenotype of prostate cancer. There was a high negative relationship between the expression level of microRNA-17-5p and circITCH in PC tissues, however, there existed a positive relationship between the expression of HOXB13 and circITCH. CircITCH acted as a sponge of miR-17-5p to increase HOXB13 gene expression. In addition, miR-17-5p overexpression or HOXB13 silencing can reduce the carcinogenic effects of circICCH in prostate cancer.

Conclusion: CircITCH promoted prostate cancer progression by regulating the HOXB13/miR-17-5p axis, and circITCH have a potential usage as therapeutic target for PC tumors.
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http://dx.doi.org/10.1186/s12935-019-0994-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892157PMC
December 2019

Two novel TSC2 mutations in renal epithelioid angiomyolipoma sensitive to everolimus.

Cancer Biol Ther 2020 10;21(1):4-11. Epub 2019 Oct 10.

The Key Laboratory of Urinary Tract Tumors and Calculi, Department of Urology Surgery, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen, China.

People who suffers renal angiomyolipoma (AML) has a low quality of life. It is widely known that genetic factors including TSC2 mutation contribute to certain populations of renal AML-bearing patients. In this study, we are the first to identify novel TSC2 mutations in one Chinese renal epithelioid AML patient: c.2652C>A; c.2688G>A based on sequencing result from biopsy tissue. These two somatic mutations cause a translational stop of TSC2, which leads to mTORC1 activation. Given the fact that activation of mTORC1 ensures cell growth and survival, we applied its inhibitor, FDA-approved everolimus, to this woman. After months of treatment with everolimus, Computer-Tomography (CT) scan results showed that everolimus successfully reduced tumor growth and distal metastasis and achieved partial response (PR) to everolimu according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). Further Blood Routine Examination results showed the concentration of red cell mass, hemoglobin, white blood cell (WBC), platelets and hematocrit (HCT) significantly returned to normal levels indicating patients with these two TSC2 mutations could be effectively treated by everolimus.
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http://dx.doi.org/10.1080/15384047.2019.1665955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012169PMC
March 2021

Overexpression of BMP1 reflects poor prognosis in clear cell renal cell carcinoma.

Cancer Gene Ther 2020 05 3;27(5):330-340. Epub 2019 Jun 3.

Department of Urology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China.

Clear cell renal cell carcinoma (ccRCC) is the highest mortality, invasion, and metastasis subtype of renal cell carcinoma. Bone morphogenetic protein (BMP) family has recently emerged as a group of cancer-related proteins in multiple pathogenesis of cancers. Currently, little is known about the prediction role of BMPs in ccRCC. Therefore, we screened The Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC) database for ccRCC patients with complete clinical information and BMP family expression data. Multivariate analysis showed that high expression of BMP1 was associated with shorter overall survival (OS) (P = 0.001), and shorter disease-free survival (DFS) (P = 0.018). Gene set enrichment analysis (GSEA) showed BMP1 was associated with epithelial-mesenchymal transition (EMT), G2M checkpoint, angiogenesis, hypoxia pathway, and Kirsten rat sarcoma viral oncogene (KRAS) signaling. Knockdown BMP1 suppressed malignancy of ccRCC in vitro and in vivo. Our results indicated that high expressions of BMP1 were poor prognostic factors and gene therapy could be an effective treatment for ccRCC.
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http://dx.doi.org/10.1038/s41417-019-0107-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237353PMC
May 2020

HAO2 inhibits malignancy of clear cell renal cell carcinoma by promoting lipid catabolic process.

J Cell Physiol 2019 12 24;234(12):23005-23016. Epub 2019 May 24.

Department of Urology, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, China.

Hydroxy acid oxidase 2 (HAO2) has been reported to inhibit tumor progression through metabolic pathway. The current study was designed to evaluate the prognostic significance and probable mechanism of HAO2 in patients with clear cell renal cell carcinoma (ccRCC). The study screened The Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC) database for patients with ccRCC having complete clinical information and HAO2 expression. Low HAO2 was associated with shorter overall survival (OS) and shorter disease-free survival (DFS). Gene set enrichment analysis (GSEA) showed HAO2 was associated with neutral lipid catabolic process, metabolic process, lipid oxidation, epithelial-mesenchymal transition (EMT), and Kirsten rat sarcoma viral oncogene signaling (KRAS). Western blot analysis and immunohistochemistry analysis checked HAO2 expression in ccRCC cancer tissues, normal tissues, and renal cancer cell lines. HAO2 was downregulated in ccRCC cancer tissues and ccRCC cell lines when compared with their control group. Overexpression of HAO2 by plasmid promoted lipid catabolic process, eliminated lipid accumulation, inhibited KRAS expression, controlled the proliferation, migration, and invasion activity of ccRCC tumor cells. Our results indicated that HAO2 inhibits malignancy ccRCC by promoting lipid catabolic process, HAO2 could be an effective molecular marker and treatment for ccRCC.
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http://dx.doi.org/10.1002/jcp.28861DOI Listing
December 2019

Effect of particle size on uranium bioleaching in column reactors from a low-grade uranium ore.

Bioresour Technol 2019 Jun 15;281:66-71. Epub 2019 Feb 15.

State Key Laboratory of Nuclear Resources and Environment, East China University of Technology, Nanchang, Jiangxi 330013, China.

This study evaluated the effectiveness of ore particle size on column bioleaching from low-grade uranium ore using an indigenous Acidithiobacillus ferrooxidans, isolated from local uranium ore. The uranium content was 0.033% by weight and ore particle size was crushed to <50 mm, <30 mm, and <15 mm. The additive content of sulfuric acid 5 g/L, Fe dosage of 5.0 g/L, spray strength of 2.57 L/(h·m) and temperature of 25 °C were controlled. After 150 days of leaching, acid consumption amounted to 2.73 g HSO per kg ore, the obtained maximum uranium extraction was 64.85% with the ore particle size of <15 mm. The results showed that a smaller particle size ore had a higher uranium extraction and that an economic uranium extraction can be obtained by correctly controlling the ore granularity.
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http://dx.doi.org/10.1016/j.biortech.2019.02.065DOI Listing
June 2019

MiR-223-3p promotes cell proliferation and metastasis by downregulating SLC4A4 in clear cell renal cell carcinoma.

Aging (Albany NY) 2019 01;11(2):615-633

Department of Urology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China.

MicroRNAs (miRNAs) are known to affect the occurrence and progression of cancer. We therefore evaluated the involvement of miR-223-3p in renal cell cancer. MiR-223-3p was highly expressed in clear cell renal cell cancer tissues. Clear cell renal cell cancer patients with higher miR-223-3p expression had higher tumor stages and grades and poorer prognoses. In renal cancer cells, overexpression of miR-223-3p enhanced cell proliferation and metastasis, while inhibition of miR-223-3p reduced the malignant capacity of the cells. MiR-223-3p was found to bind directly to solute carrier family 4, member 4 () mRNA, thereby reducing SLC4A4 mRNA and protein expression. SLC4A4 overexpression restrained cell proliferation and metastasis by suppressing Kirsten rat sarcoma viral oncogene (KRAS) expression in renal cancer cells. expression correlated negatively with miR-223-3p expression in patient samples. Given that miR-223-3p suppressed the SLC4A4/KRAS axis, miR-223-3p gene therapy could be an effective treatment for renal cancer.
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http://dx.doi.org/10.18632/aging.101763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366987PMC
January 2019

TRIM2 downregulation in clear cell renal cell carcinoma affects cell proliferation, migration, and invasion and predicts poor patients' survival.

Cancer Manag Res 2018 20;10:5951-5964. Epub 2018 Nov 20.

Department of Urology, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China,

Background And Aim: Tripartite motif containing (TRIM) family protein has been involved in multiple pathogenesis of cancers. TRIM2 is a member of the family, and its role in clear cell renal cell carcinoma (ccRCC) remains to be unclarifid. Here, we showed the clinical value and biological role of TRIM2 in ccRCC.

Methods: ROC curves analyzed the clinicopathological parameters, Kaplan-Meier survival analysis determined the correlation of OS and DFS time, multivariate analysis demonstrated the prognostic indicator in overall survival and disease-free survival of ccRCC with TRIM2 expression in The Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC) database. Western blotting and immunohistochemistry were used to check the level of TRIM2 expression. Gain-of-function assay by exogenous overexpression of TRIM2 studied the biological role of TRIM2 in renal cell carcinoma cells.

Results: TRIM2 expression was associated with various clinicopathologicalfactors and lower TRIM2 expression was interrelated to a poor prognosis. The levels of TRIM2 expression were also scanty in ccRCC tissues and renal cancer cell lines than in normal control. The biological role of TRIM2 in ccRCC was identifid by bioinformatics analysis and functional analysis. Exogenous overexpression of TRIM2 with the gain-of-function assay in renal cell carcinoma cells showed that the cell proliferation, migration, and invasion were signifiantly suppressed.

Conclusion: These results showed that TRIM2 acted as an antitumor gene and a specifi prognostic indicator for patients with ccRCC, which indicated that positive modulation of TRIM2 might be a novel treatment strategy for ccRCC.
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http://dx.doi.org/10.2147/CMAR.S185270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255054PMC
November 2018

miR-29b negatively regulates MMP2 to impact gastric cancer development by suppress gastric cancer cell migration and tumor growth.

J Cancer 2018 1;9(20):3776-3786. Epub 2018 Oct 1.

Department of Gastrointestinal Surgery, Zhongshan Hospital affiliated to Xiamen University, Xiamen, China 361004.

MicroRNAs (miRNAs) are important regulators and associated with the development of many different types of cancer, including gastric cancer. However, their pathophysiologic role and their relevance to tumorigenesis, invasion and metastasis are still unknown. In our current study, we performed microRNA array and found that 28 of miRNAs were differentially expressed in INF type of gastric cancer. Among 28 miRNAs, miR-29b was one of the most significantly down-regulated miRNA. Further bioinformatics analysis showed that MMP2 was a potential target of miR-29b. Interestingly, luciferase analysis showed that miR-29b negatively regulates MMP2 by binding with the miRNA response element (MRE) on the 3'UTR of MMP2. In addition, overexpression of miR-29b significantly decreased the mRNA and protein level of MMP2 and the activity of MMP2 to suppress gastric cancer cell migration. Moreover, lentivirus mediated overexpression of miR-29b dramatically suppressed the ability of BGC823 cells to form colonies and their ability to develop tumor in nude mice. Finally, our qPCR and western blot analysis showed that miR-29b was significantly reduced in clinical gastric cancer tissue, whereas MMP2 protein was significantly up-regulated, suggesting that this aberrant down-regulation of miR-29b might be associated with the abnormal regulation of MMP2 and the development of gastric cancer. Significant apparent was also found between miR-29b expression and TNM staging, lymph node status, tumor differentiation and Ming classification. Together, our data suggest an important regulatory role of miR-29b in the development of gastric cancer. Thus, miR-29b and MMP2 might be important diagnostic or therapeutic targets for human tumor diseases.
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http://dx.doi.org/10.7150/jca.26263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6216010PMC
October 2018

Serum exosomal miR-210 as a potential biomarker for clear cell renal cell carcinoma.

J Cell Biochem 2018 Oct 10. Epub 2018 Oct 10.

Department of Urology, The First Affiliated Hospital of Xiamen University, The First Clinical College of Fujian Medical University, Xiamen, Fujian, China.

Exosomal microRNAs (miRNAs) are suggested to reflect molecular changes occurring in their cells of origin and are potential indicators in the early detection of cancers. This study aimed to determine whether certain exosomal miRNAs from tumor tissue can be used as noninvasive biomarkers for clear cell renal cell carcinoma (ccRCC). Based on ccRCC miRNA expression profiles and the literature, we selected six miRNAs (miR-210, miR-224, miR-452, miR-155, miR-21, and miR-34a) and analyzed their expression in tissues, sera, and serum exosomes through quantitative real-time polymerase chain reaction in hypoxia-induced (with CoCl ) renal cell lines. miR-210, miR-224, miR-452, miR-155, and miR-21 were upregulated in tumor tissues compared with normal tissues. Serum miR-210 and miR-155 levels were higher in patients with ccRCC than in healthy controls (HCs). Furthermore, only exosomal miR-210 was significantly upregulated in patients with ccRCC than in HCs. Moreover, receiver operating characteristic (ROC) curve analysis revealed an area under the ROC curve of 0.8779 (95% confidence interval, 0.7987-0.9571) and a sensitivity and specificity of 82.5% and 80.0%, respectively. Moreover, exosomal miR-210 was upregulated at an advanced stage, and Fuhrman grade and metastasis decreased significantly one month after surgery. Acute hypoxia exposure activates miR-210 and release of exosomes with upregulated miR-210 in both normal and tumor RCC cell lines and interferes with vacuole membrane protein 1 mRNA expression, especially in the metastatic ccRCC cell line. In conclusion, Serum exosomal miR-210 originating from tumor tissue has potential as a novel noninvasive biomarker for the detection and prognosis of ccRCC.
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http://dx.doi.org/10.1002/jcb.27347DOI Listing
October 2018

Ternary semiconductor metal oxide blends grafted [email protected] hybrid as dimensionally stable anode active layer for photoelectrochemical oxidation of organic compounds: Design strategies and photoelectric synergistic mechanism.

J Hazard Mater 2019 Jan 14;362:336-347. Epub 2018 Sep 14.

State Key Laboratory Breeding Base of Nuclear Resources and Environment, East China University of Technology, Nanchang City, Jiangxi 330013, PR China; School of Water Resource & Environmental Engineering, East China University of Technology, Nanchang City, Jiangxi 330013, PR China.

The development of ultra-efficient, sustainable, and easily accessible anode with relative non-precious semiconducting metal oxides is highly significant for application in the practical treatment of organically polluted water. Herein, we report SnO, TiO, and AgO ternary semiconductor metal oxide blend grafted [email protected] hybrids, prepared with the one-step sol-gel method and applied as a dimensionally stable anode (DSA)-active layer on a SnO-Sb/Ti electrode. Factors affecting crystal formation, including the presence or absence of O during calcination, the calcination temperature, and [email protected] additive dosage were discussed. The micromorphology, phase composition, and photoelectrochemical activity of the newly designed anode were comprehensively characterized. The optimized preparation, which yielded a solid-solution structure with flat and smooth surface and well-crystallized lattice configuration, occurred in the absence of O during calcination at 550 ℃ with an [email protected] additive dosage of 0.2 g in the sol-gel precursor. The newly designed DSA displayed improved electrocatalysis (EC) and photoelectrical catalysis (PEC) capacity. The phenol and its TOC removal efficiency reached 90.65% and 58.17% for 10 mA/cm current density with a metal halide lamp in 3 h. The lifespan was four times that of SnO-Sb/Ti electrode. This proposed DSA construction strategy may support improved EC and PEC reactivities toward the decomposition of organic pollutants.
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http://dx.doi.org/10.1016/j.jhazmat.2018.09.041DOI Listing
January 2019

Circular RNA CEP128 acts as a sponge of miR-145-5p in promoting the bladder cancer progression via regulating SOX11.

Mol Med 2018 07 31;24(1):40. Epub 2018 Jul 31.

Department of Urology, the First Affiliated Hospital of Xiamen University, No.55 Zhenhai Road, Xiamen, 361003, Fujian, China.

Background: This study aimed to investigate the effect of over-expressing circular RNA CEP128 (circCEP128) on cell functions and explore the molecular mechanism of which in bladder carcinoma.

Methods: The differentially expressed circRNAs and mRNAs in bladder carcinoma cells and cells in adjacent tissues were screened out using microarray analysis. Expression levels of circRNAs and mRNAs in tissues and cells were determined by qRT-PCR. Expression of SOX11 was detected by western blot. Luciferase reporter assay and RNA pull-down assay were used to investigate the interactions between the specific circRNA, miRNA and mRNA. Cell cycle and apoptosis were measured using flow cytometry after transfection. MTT assay was also performed to detect the cell proliferation.

Results: In present study, circCEP128 and SOX11 were observed significantly up-regulated in bladder cancer tissues, while the expression of miR-145-5p was decreased in cancer samples compared to normal samples. Cytoscape was used to visualize circCEP128-miRNA-target gene interactions based on the TargetScan and circular RNA interactome, which revealed that circCEP128 served as a sponge of miR-145-5p and indirectly regulated SOX11. Knockdown of circCEP128 induced the inhibition of cell proliferation and the increased bladder cancer cell apoptosis rate.

Conclusions: CircCEP128 functions as a ceRNA for miR-145-5p, which could up regulates SOX11 and further promotes cell proliferation and inhibits cell apoptosis of bladder cancer.
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http://dx.doi.org/10.1186/s10020-018-0039-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6069875PMC
July 2018

miR-224/miR-141 ratio as a novel diagnostic biomarker in renal cell carcinoma.

Oncol Lett 2018 Aug 1;16(2):1666-1674. Epub 2018 Jun 1.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

Biomarkers to guide the clinical treatment of patients with renal cell carcinoma (RCC) are not yet routinely available. MicroRNAs (miRNAs) have been demonstrated to serve as biomarkers for a number of types of cancer. Based on a previous study by this group, we hypothesize that several highly differentially expressed miRNAs may serve as tissue and plasma biomarkers in patients with RCC. The expression levels of miR-210, miR-224 and miR-141 were analyzed in tissue samples from the same cohort of 78 patients with RCC, in paired pre- and post-operative plasma samples from 66 patients with clear cell RCC (ccRCC) and in 67 healthy controls by reverse transcription-quantitative polymerase chain reaction. Receiver operating characteristic (ROC) was used to evaluate the diagnostic accuracy associated with the expression of miR-210, miR-224 and miR-141. ROC curves revealed that the diagnostic accuracy (area under the curve) of tissue miR-210, miR-224, the ratio of miR-210/miR-141 (miR), miR-224/miR-141 (miR) and miR-210× miR-224/miR-141 (miR) in ccRCC was 0.8329, 0.8511, 0.9412, 0.9898 and 0.9771, respectively. Notably, miR demonstrated the highest accuracy among these miRNAs for discriminating ccRCC tissues from normal tissues, with a sensitivity of 97.06% and a specificity of 98.53%. The expression levels of plasma miR-210 and miR-224 were significantly increased in patients compared with healthy control patients, and were reduced postoperatively (P<0.05). The diagnostic accuracy of plasma miR-210 and miR-224 were 0.6775 (89.55% sensitivity and 48.48% specificity) and 0.6056 (88.06% sensitivity and 40.91% specificity), respectively. The present study indicated that the tissue miR-224/miR-141 ratio is a potentially powerful tool for detecting ccRCC. However, plasma miR-210 and miR-224 may not be associated with diagnosis of ccRCC.
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http://dx.doi.org/10.3892/ol.2018.8874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036413PMC
August 2018

Highly Efficient Interception and Precipitation of Uranium(VI) from Aqueous Solution by Iron-Electrocoagulation Combined with Cooperative Chelation by Organic Ligands.

Environ Sci Technol 2017 Dec 12;51(24):14368-14378. Epub 2017 Dec 12.

State Key Laboratory Breeding Base of Nuclear Resources and Environment, East China University of Technology , Nanchang City, Jiangxi 330013, PR China.

A new strategy combining iron-electrocoagulation and organic ligands (OGLs) cooperative chelation was proposed to screen and precipitate low concentrations (0-18.52 μmol/L) of uranium contaminant in aqueous solution. We hypothesized that OGLs with amino, hydroxyl, and carboxyl groups hydrophobically/hydrophilically would realize precuring of uranyl ion at pH < 3.0, and the following iron-electrocoagulation would achieve faster and more efficient uranium precipitation. Experimentally, the strategy demonstrated highly efficient uranium(VI) precipitation efficiency, especially with hydrophilic macromolecular OGLs. The uranium removal efficiency at optimized experimental condition reached 99.65%. The decrease of zeta potential and the lattice enwrapping between U-OGLs chelates and flocculation precursor were ascribed to the enhanced uranium precipitation activity. Uranium was precipitated as oxides of U(VI) or higher valences that were easily captured in aggregated micelles under low operation current potential. The actual uranium tailing wastewater was treated, and a satisfied uranium removal efficiency of 99.02% was discovered. After elution of the precipitated flocs, a concentrated uranium solution (up to 106.52 μmol/L) with very few other metallic impurities was obtained. Therefore, the proposed strategy could remove uranium and concentrate it concurrently. This work could provide new insights into the purification and recovery of uranium from aqueous solutions in a cost-effective and environmentally friendly process.
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http://dx.doi.org/10.1021/acs.est.7b05288DOI Listing
December 2017

Enhanced photocatalytic reduction activity of uranium(vi) from aqueous solution using the FeO-graphene oxide nanocomposite.

Dalton Trans 2017 Nov;46(43):14762-14770

State Key Laboratory Breeding Base of Nuclear Resources and Environment, East China University of Technology, Nanchang, 330013, China.

Photocatalytic technologies are a potential solution for remediation of radioactive wastewater, including the reduction of radioactive hexavalent uranium, which is commonly found in wastewater from the nuclear industry. In this study, FeO-graphene oxide composites were synthesized by an easy and scalable impregnation method as a catalyst for the reduction of U(vi). X-ray photoelectron spectroscopy analysis and high-resolution transmission electron microscopy images of this composite clearly showed that the FeO nanoparticles exist in the layered structure of graphene oxide. The photocatalytic activity of the FeO-graphene oxide composite was evaluated by the reduction of U(vi) to U(iv) in aqueous solution under visible light. The results showed that the photocatalytic process of the FeO-graphene oxide composite was always faster than that of the FeO nanoparticles. Moreover, the experimental kinetic data for the catalytic process followed a pseudo-first-order model. The stability of the FeO-graphene oxide composites was studied over successive experiments, with the photocatalytic reduction efficiency of U(vi) decreasing to 76.0% after four cycles. Based on these experimental results, the enhanced photocatalytic activity and stability of FeO-graphene oxide composites can be attributed to the improved adsorption properties of U(vi) at GO and the electron transfer from iron oxide to GO.
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http://dx.doi.org/10.1039/c7dt02639kDOI Listing
November 2017

Enhanced decolorization of methyl orange in aqueous solution using iron-carbon micro-electrolysis activation of sodium persulfate.

Chemosphere 2017 Aug 5;180:100-107. Epub 2017 Apr 5.

School of Environment Science and Spatial Informatics, China University of Mining and Technology, Xuzhou 221008, PR China.

Reactivity of sodium persulfate (PS) in the decolorization of methyl orange (MO) in aqueous solution using an iron-carbon micro-electrolysis (ICE) method was investigated. The effects of sodium persulfate doses, pH, Fe-to-C mass ratios, initial MO concentration as well as the reaction temperature were comprehensively studied in batch experiments. The ICE-PS coupled process was more suitable for wide ranges of pH, initial MO concentration and reaction temperature, accompanied by the reduction of Fe compared ICE. The MO removal efficiency improved substantially by ICE-PS technique, 76.03% for ICE and 91.27% for ICE-PS at experimental conditions of pH 3.0, Fe-to-C mass ratio 3:1, PS addition 10 mM and initial MO concentration 0.61 mM. Furthermore, the biodegradability index (BI) dramatically increased from 0.26 to 0.65. The binary hydroxyl and sulfate radicals that non-selectively degrade MO to the derivatives with small molecules are ascribed to ICE-PS method as detected by the UV-vis spectra. The PS activation resource was Fe through the hydroxyl radical quenching reaction by the additive tert-butanol (TBA). This study provides an in-depth theoretical understanding of the development and wide commercial application of the ICE technology to refractory industrial dye wastewater treatment.
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http://dx.doi.org/10.1016/j.chemosphere.2017.04.019DOI Listing
August 2017

AgPO/rectorite nanocomposites: Ultrasound-assisted preparation, characterization and enhancement of stability and visible-light photocatalytic activity.

Ultrason Sonochem 2017 01 25;34:831-838. Epub 2016 Jul 25.

School of Water Resources & Environmental Engineering, East China University of Technology, Nanchang 330013, China.

To overcome the drawback of low stable brought by the transformation of Ag into Ag, a highly efficient and stable photocatalyst AgPO/rectorite composite was successfully synthesized by ultrasound-assisted precipitation method. The as-prepared samples were characterized by field-emission scanning electron microscopy, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, N adsorption-desorption, room-temperature photoluminescence spectra, Fourier transform infrared spectrum measurements and UV-vis diffuse reflectance spectra. The absorption edges of the AgPO/rectorite display a noticeable shift to the visible light region as compared to that of the AgPO. Compared with bare AgPO, the AgPO/rectorite composite by ultrasound-assisted precipitation process exhibits significantly enhanced photocatalytic activity and stable for methyl orange (MO) degradation under visible light irradiation. The improved activity of the AgPO/rectorite photocatalyst could be attributed to the expanded visible light absorption, the enhanced interfacial charge transfer and the inhibited recombination of electron-hole pairs. Therefore, the facile ultrasound-assisted preparation process provides some insight into the application of AgPO/rectorite nanocomposites in photocatalytic degradation of organic pollutants.
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http://dx.doi.org/10.1016/j.ultsonch.2016.07.017DOI Listing
January 2017

miR-200c Targets CDK2 and Suppresses Tumorigenesis in Renal Cell Carcinoma.

Mol Cancer Res 2015 Dec 6;13(12):1567-77. Epub 2015 Aug 6.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.

Unlabelled: miRNA expression profiles are widely investigated in the major cancers, but their specific roles and functions in cancers have not yet to be fully elucidated. In this study, miRNA expression profiles were determined in clear cell renal cell carcinomas (ccRCC) and in matched normal kidney tissues by using a miRNA microarray platform which covers a total of 851 human miRNAs. Differential expression of 74 miRNAs were identified between ccRCC specimens and their matched adjacent noncancerous tissues, of which 30 were significantly upregulated in ccRCCs, and the other 44 were downregulated (fold change ≥ 2, P < 0.05). Interestingly, miR-200c was commonly downregulated in ccRCC specimens and ccRCC cell lines with significant functional consequences. Growth curve and FACS assay indicated that overexpression of miR-200c suppressed cell growth and induced cell-cycle arrest at G0-G1 phases in SN12-PM6 and 786-O cells. Furthermore, miR-200c could suppress in vivo tumor growth of SN12-PM6 cells in mice. Bioinformatics exposed cyclin-dependent kinase 2 (CDK2) as a potential target of miR-200c, which was validated using a luciferase reporter assay. Mechanistic investigations revealed that miR-200c was directly responsible for suppressing the expression of CDK2 in ccRCC cell lines and xenografts. Taken together, miR-200c plays an antioncogenic role in ccRCC, through controlling cell growth and cell-cycle progression by downregulating the G1-S regulator CDK2.

Implications: miR-200c exerts its novel antioncogenic function in renal cell carcinoma by controlling CDK2-dependent cell growth and cell-cycle progression.
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http://dx.doi.org/10.1158/1541-7786.MCR-15-0128DOI Listing
December 2015

[Magnetic resonance image fusion based on three dimensional band limited shearlet transform].

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2015 Feb;32(1):181-6, 196

More and more medical devices can capture different features of human body and form three dimensional (3D) images. In clinical applications, usually it is required to fuse multiple source images containing different and crucial information into one for the purpose of assisting medical treatment. However, traditional image fusion methods are normally designed for two dimensional (2D) images and will lead to loss of the third dimensional information if directly applied to 3D data. Therefore, a novel 3D magnetic image fusion method was proposed based on the combination of newly invented beyond wavelet transform, called 3D band limited shearlet transformand (BLST), and four groups of traditional fusion rules. The proposed method was then compared with the 2D and 3D wavelet and dual-tree complex wavelet transform fusion methods through 4 groups of human brain T2* and quantitative susceptibility mapping (QSM) images. The experiments indicated that the performance of the method based on 3D transform was generally superior to the existing methods based on 2D transform. Taking advantage of direction representation, shearlet transform could effectively improve the performance of conventional fusion method based on 3D transform. It is well concluded, therefore, that the proposed method is the best among the methods based on 2D and 3D transforms.
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February 2015

miR-129-3p, as a diagnostic and prognostic biomarker for renal cell carcinoma, attenuates cell migration and invasion via downregulating multiple metastasis-related genes.

J Cancer Res Clin Oncol 2014 Aug 7;140(8):1295-304. Epub 2014 May 7.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, People's Republic of China.

Purpose: Downregulation of miRNA expression has been identified as a novel feature of renal cell carcinoma (RCC). Recently, miR-129-2 is well known to be frequently reduced by DNA methylation and has anti-tumor effects in various tumors but so far not in RCC. The aim of this study was to investigate the clinical significance and the role of it in RCC.

Methods: The expression levels of miR-129-3p and miR-129-5p, two mature products of miR-129-2, were determined by real-time quantitative reverse transcription PCR in 69 cases of paired different kidney tumors and normal tissues and clear cell RCC (ccRCC) cell lines. The roles of them in RCC cells were assessed by functional analyses. Protein expression was detected by Western blot.

Results: miR-129-3p, but not miR-129-5p, was widely attenuated in human ccRCC, and chromophobe RCC. miR-129-3p could yield 73.5 % accuracy in discriminating ccRCCs from normal tissues. The relative miR-129-3p expression significantly differed between malignant and benign kidney tumors. Importantly, low miR-129-3p levels were associated with short disease-free and overall survival. Ectopic expression of miR-129-3p robustly impaired RCC cell migratory and invasive properties, but had no impact on cell viability and cell cycle distribution. Finally, miR-129-3p decreased multiple metastasis-related genes in RCC cells, including SOX4, phosphorylation of focal adhesion kinase and MMP-2/9 expression.

Conclusions: miR-129-3p may act as a promising diagnostic biomarker for discriminating ccRCC from benign tumors and normal tissues and an independent prognostic biomarker in ccRCC. miR-129-3p may exert its anti-metastatic function through modulating multiple targets.
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http://dx.doi.org/10.1007/s00432-014-1690-7DOI Listing
August 2014

miR-141 is a key regulator of renal cell carcinoma proliferation and metastasis by controlling EphA2 expression.

Clin Cancer Res 2014 May 19;20(10):2617-30. Epub 2014 Mar 19.

Authors' Affiliations: Department of Urology, Union Hospital; Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Cancer Biology Program, Hematology-Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; and Department of Neurology, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Georgia Regents University, Augusta, Georgia

Purpose: Although microRNAs (miRNA) have been revealed as crucial modulators of tumorigenesis, our understanding of their roles in renal cell carcinoma (RCC) is limited. Here we sought to identify human miRNAs that act as key regulators of renal carcinogenesis.

Experimental Design: We performed microarray-based miRNA profiling of clear cell RCC (ccRCC) and adjacent normal tissues and then explored the roles of miR-141 both in vitro and in vivo, which was the most significantly downregulated in ccRCC tissues.

Results: A total of 74 miRNAs were dysregulated in ccRCC compared with normal tissues. miR-141 was remarkably downregulated in 92.6% (63/68) ccRCC tissues and would serve as a promising biomarker for discriminating ccRCC from normal tissues with an area under the receiver operating characteristics curve of 0.93. Overexpression of miR-141 robustly impaired ccRCC cell migratory and invasive properties and suppressed cell proliferation by arresting cells at G0-G1 phase in vitro and in human RCC orthotopic xenografts. Significantly, the antitumor activities of miR-141 were mediated by its reversal regulation of erythropoietin-producing hepatocellular (Eph) A2 (EphA2), which then relayed a signaling transduction cascade to attenuate the functions of focal adhesion kinase (FAK), AKT, and MMP2/9. In addition, a specific and inverse correlation between miR-141 and EphA2 expression was obtained in human ccRCC samples. Finally, miR-141 could be secreted from the ccRCC donor cells, and be taken up and function moderately in the ccRCC recipient cells.

Conclusion: miR-141 serves as a potential biomarker for discriminating ccRCC from normal tissues and a crucial suppressor of ccRCC cell proliferation and metastasis by modulating the EphA2/p-FAK/p-AKT/MMPs signaling cascade.
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http://dx.doi.org/10.1158/1078-0432.CCR-13-3224DOI Listing
May 2014

Inhibition of PP2A activity confers a TRAIL-sensitive phenotype during malignant transformation.

Mol Cancer Res 2014 Feb 2;12(2):217-27. Epub 2013 Dec 2.

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, Hubei Province, China.

Unlabelled: TRAIL is a promising anticancer agent because it induces apoptosis in the majority of human cancer cells but spares the normal cells. To determine the mechanistic nature of how normal cells acquire a TRAIL-sensitive phenotype during the process of malignant transformation, an experimental cell system was developed by sequential introduction of human telomerase reverse transcriptase and SV40 T antigens (large and small) into normal human prostatic epithelial cells (PrEC). This model system demonstrated that inhibition of protein phosphatase 2A (PP2A), either by SV40 small T antigen, okadaic acid, Calyculin A, or PP2A catalytic subunit siRNA, sensitized normal human PrEC and immortalized cells to TRAIL-induced apoptosis. Moreover, sensitization occurred during the premalignant period of tumorigenesis and PP2A exerted its antiapoptotic activity by negatively regulating c-Fos/AP-1. In addition, low-dose okadaic acid treatment sensitized TRAIL-resistant cancer cells to TRAIL, suggesting that PP2A inhibitors could be used as an enhancer of apoptosis induced by TRAIL or TRAIL-like agents. These data indicate that downregulation of PP2A activity is a critical step for normal cells to acquire a TRAIL-sensitive phenotype during tumorigenesis and that the level of PP2A activity may foretell cellular sensitivity to TRAIL-induced apoptosis.

Implications: Inhibition of PP2A is a key determinant in acquiring TRAIL sensitivity during tumorigenesis, with c-Fos/AP-1 as an essential mediator.
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http://dx.doi.org/10.1158/1541-7786.MCR-13-0441DOI Listing
February 2014

microRNA-200c modulates the epithelial-to-mesenchymal transition in human renal cell carcinoma metastasis.

Oncol Rep 2013 Aug 7;30(2):643-50. Epub 2013 Jun 7.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, PR China.

microRNAs (miRNAs) play essential roles in several physiological and pathological processes, including tumor metastasis. Metastasis is associated with poor prognosis in renal carcinoma patients and almost 20-30% of patients present with distant metastasis at the time of diagnosis. The aim of the present study was to investigate the possible roles of miR-200c in regulating metastasis and to identify its target genes in renal cell carcinoma (RCC). Among the miRNAs downregulated in our tissue specimen microarray, miR-200c was downregulated significantly. Functional assays demonstrated that restoration of miR-200c significantly inhibited the migration and invasion of SN12-PM6 and 786-0 cells in vitro. Genome-wide gene expression analysis and TargetScan database studies showed that ZEB1, which has been shown to promote tumor invasion and migration through E-cadherin gene silencing, is a promising candidate target gene of miR‑200c. Overexpression of miR-200c in SN12-PM6 and 786-0 cells was concurrent with downregulation of ZEB1 and upregulation of E-cadherin mRNA and protein. In addition, miR-200c affected the protein expression of p-Akt and Akt. Thus, our study demonstrated that miR-200c decreases the metastatic ability of renal carcinoma cells by upregulating E-cadherin through ZEB1 and that modulating the expression of miR-200c could influence Akt protein levels. We therefore concluded that there is an Akt-miR-200c-E-cadherin axis in the epithelial-to-mesenchymal transition process in RCC.
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http://dx.doi.org/10.3892/or.2013.2530DOI Listing
August 2013

Simultaneous removal of phenanthrene and lead from artificially contaminated soils with glycine-β-cyclodextrin.

J Hazard Mater 2010 Dec 27;184(1-3):690-695. Epub 2010 Aug 27.

School of Resources and Environmental Science, Wuhan University, Wuhan 430079, Hubei, PR China.

Preparation of glycine-β-cyclodextrin (GCD) was carried out by the reaction of β-cyclodextrin with glycine in the presence of KOH and epichlorohydrin. The enhanced solubilization behavior of phenanthrene and lead carbonate by GCD was studied, and the desorption behavior of phenanthrene and lead from co-contaminated soil was also investigated. The results showed that GCD has obvious solubilization for phenanthrene and lead carbonate. The solubility of phenanthrene in 30 g/L of GCD was enhanced about 30-fold. And the apparent aqueous solubilities of lead carbonate are also obviously increased with increasing GCD concentration, when the concentration of GCD reached 20 g/L, the aqueous lead concentration was 2945 mg/L. GCD could simultaneously increase the apparent aqueous solubility of phenanthrene and complex with lead. The desorption process of GCD for phenanthrene and lead from co-contaminated soil followed the pseudo-second-order kinetic model. The removal efficiencies of phenanthrene and lead in soil increased dramatically with increasing GCD concentrations. At concentration of 40 g/L, GCD has a removal efficiency of 85.8% and 78.8% for lead and phenanthrene, respectively, from the combined contaminated soil. The use of GCD as an extractant to enhance the removal of heavy and hydrophobic organic contaminants (HOCs) from co-contaminated soils appears as a promising remediation method.
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http://dx.doi.org/10.1016/j.jhazmat.2010.08.094DOI Listing
December 2010
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