Publications by authors named "Ming-Zhong Sun"

65 Publications

The potential role of miR-124-3p in tumorigenesis and other related diseases.

Mol Biol Rep 2021 Apr 20. Epub 2021 Apr 20.

Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA, 01610, USA.

MicroRNAs (miRNAs) are a class of single-stranded noncoding and endogenous RNA molecules with a length of 18-25 nucleotides. Previous work has shown that miR-124-3p leads to malignant progression of cancer including cell apoptosis, migration, invasion, drug resistance, and also recovers neural function, affects adipogenic differentiation, facilitates wound healing through control of various target genes. miR-124-3p has been mainly previously characterized as a tumor suppressor regulating tumorigenesis and progression in several cancers, such as hepatocellular carcinoma (HCC), gastric cancer (GC), bladder cancer, ovarian cancer (OC), and leukemia, as a tumor promotor in breast cancer (BC), and it has been also widely studied in a variety of neurological diseases, like Parkinson's disease (PD), dementia and Alzheimer's disease (AD), and cardiovascular diseases, ulcerative colitis (UC), acute respiratory distress syndrome (ARDS). To lay the groundwork for future therapeutic strategies, in this review we mainly focus on the most recent years of literature on the functions of miR-124-3p in related major cancers, as well as its downstream target genes. Although current work as yet provides an incomplete picture, miR-124-3p is still worthy of more attention as a practical and effective clinical biomarker.
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http://dx.doi.org/10.1007/s11033-021-06347-4DOI Listing
April 2021

CRKL promotes hepatocarcinoma through enhancing glucose metabolism of cancer cells via activating PI3K/Akt.

J Cell Mol Med 2021 Mar 1;25(5):2714-2724. Epub 2021 Feb 1.

Department of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.

Abnormal glucose metabolism may contribute to cancer progression. As a member of the CRK (v-crk sarcoma virus CT10 oncogene homologue) adapter protein family, CRKL (CRK-like) associated with the development and progression of various tumours. However, the exact role and underlying mechanism of CRKL on energy metabolism remain unknown. In this study, we investigated the effect of CRKL on glucose metabolism of hepatocarcinoma cells. CRKL and PI3K were found to be overexpressed in both hepatocarcinoma cells and tissues; meanwhile, CRKL up-regulation was positively correlated with PI3K up-regulation. Functional investigations revealed that CRKL overexpression promoted glucose uptake, lactate production and glycogen synthesis of hepatocarcinoma cells by up-regulating glucose transporters 1 (GLUT1), hexokinase II (HKII) expression and down-regulating glycogen synthase kinase 3β (GSK3β) expression. Mechanistically, CRKL promoted glucose metabolism of hepatocarcinoma cells via enhancing the CRKL-PI3K/Akt-GLUT1/HKII-glucose uptake, CRKL-PI3K/Akt-HKII-glucose-lactate production and CRKL-PI3K/Akt-Gsk3β-glycogen synthesis. We demonstrate CRKL facilitates HCC malignancy via enhancing glucose uptake, lactate production and glycogen synthesis through PI3K/Akt pathway. It provides interesting fundamental clues to CRKL-related carcinogenesis through glucose metabolism and offers novel therapeutic strategies for hepatocarcinoma.
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http://dx.doi.org/10.1111/jcmm.16303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933966PMC
March 2021

Taurine improves neuron injuries and cognitive impairment in a mouse Parkinson's disease model through inhibition of microglial activation.

Neurotoxicology 2021 03 12;83:129-136. Epub 2021 Jan 12.

Department of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, China. Electronic address:

Clinical and experimental findings support the view that activation of hippocampus microglia through NADPH oxidase contributes to cognitive impairment in Parkinson's disease (PD). Taurine, an antioxidant, displays an exclusive physical property on brain function, such as learning and memory. To date, the role of taurine in improving cognitive impairment in PD is not fully uncovered. Hence, we evaluated the protective effect of taurine on cognitive ability and explored the related mechanism in the model built by paraquat and maneb (P + M)-induced PD mice. Then the ability of learning and memory was observed by Morris water maze, neuron loss was evaluated by immunohistochemistry in hippocampus, the level of postsynaptic density 95 (PSD95) and microglia activation was assessed by immunostaining, the molecules (gp91, p47, mac1, p-Src/Src and p-Erk/Erk) were examined by western blot. The results showed that taurine could alleviate the impairments in learning and memory induced by P + M injection in mice (decreased escape latency on day 4, P < 0.01; decreased swimming distance on day 4, P < 0.05; increased percent time in target quadrant, P < 0.05), corresponding with activation of microglia (decreased IBa-1 density, P < 0.001; decreased the protein expression of p47, P < 0.05; decreased protein expression of gp91, P < 0.01; decreased p-Src/Src, P < 0.01; decreased p-Erk/Erk, P < 0.01; decreased mac 1, P < 0.01), decreased neuron loss (increased number of NeurN neuron, P < 0.001; increased protein expression of NeruN, P < 0.01; decreased protein expression of caspase 3, P < 0.01) and increased PSD95 level in hippocampus (P < 0.01). The results indicated that mac1 and Src-Erk signaling was involved in increased NADPH oxidase expression in hippocampus microglia of P + M mice, and taurine could improve injuries in learning and memory through mac1 reduction. The new findings in mac1 triggering hippocampal microglia NADPH oxidase through Src/Erk pathway of the present study might provide a therapy target for PD.
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http://dx.doi.org/10.1016/j.neuro.2021.01.002DOI Listing
March 2021

miR-124-3p Suppresses the Invasiveness and Metastasis of Hepatocarcinoma Cells Targeting CRKL.

Front Mol Biosci 2020 15;7:223. Epub 2020 Sep 15.

Department of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.

Abnormal expressions of microRNAs are involved in growth and progression of human cancers including hepatocellular carcinoma (HCC). An adaptor protein CRKL plays a pivotal role in HCC growth, whereas miR-124-3p downregulation is associated with clinical stage and the poor survival of patients. However, the relationship between miR-124-3p and CRKL and the molecular mechanisms through which they regulate HCC metastasis remains unclear. In the current work, we explored miR-124-3p and its correlation with CRKL expression in HCC patient tissues. We found that miR-124-3p deficiency is inversely co-related with CRKL overexpression in tumorous tissues of HCC patients, which was also consistent in HCCLM3 and Huh7 HCC cell lines. Target validation data shows that miR-124-3p directly targets CRKL. The overexpression of miR-124-3p reverses the CRKL expression at both mRNA and protein levels and inhibits the cell development, migration, and invasion. Mechanistic investigations showed that CRKL downregulation suppresses the ERK pathway and EMT process, and concomitant decrease in invasion and metastasis of HCC cells. The expressions of key molecules in the ERK pathway such as RAF, MEK, ERK1/2, and pERK1/2 and key promoters of EMT such as -cadherin and vimentin were downregulated, whereas -cadherin, a key suppression indicator of EMT, was upregulated. MiR-124-3p-mediated CRKL suppression led to BAX/BCL-2 increase and C-JUN downregulation, which inhibited the cell proliferation and promoted the apoptosis in HCC cells. Collectively, our data illustrates that miR-124-3p acts as an important tumor-suppressive miRNA to suppress HCC carcinogenesis through targeting CRKL. The miR-124-3p-CRKL axial regulated pathway may offer valuable indications for cancer research, diagnosis, and treatment.
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http://dx.doi.org/10.3389/fmolb.2020.00223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522612PMC
September 2020

miR-429-CRKL axis regulates clear cell renal cell carcinoma malignant progression through SOS1/MEK/ERK/MMP2/MMP9 pathway.

Biomed Pharmacother 2020 Jul 12;127:110215. Epub 2020 May 12.

Department of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China. Electronic address:

The pathogenesis and tumorigenesis of clear cell renal cell carcinoma (ccRCC) remain unclear. The deregulations of miR-429, a member of miR-200 family, and v-crk sarcoma virus CT10 oncogene homologue (avian)-like (CRKL), an adaptor protein of CRK family, are involved in the development, metastasis and prognosis of various cancers. Current study aimed to demonstrate the differential expressions of miR-429 and CRKL with their correlationship and molecular regulation mechanism in ccRCC malignancy. miR-429 and CRKL separately showed suppressing and promoting effects in ccRCC. Lower miR-429 expression and higher CRKL expression were negatively correlated in surgical cancerous tissues by promoting the advance of ccRCC. By binding to the 3'-UTR of CRKL, miR-429 reversely regulated CRKL for its functionalities in ccRCC cells. CRKL knockdown and overexpression separately decreased and increased the in vitro migration and invasion of 786-O cells, which were consistent with the influences of miR-429 overexpression and knockdown on 786-O through respectively downregulating and upregulating CRKL via SOS1/MEK/ERK/MMP2/MMP9 pathway. The enhancements of CRKL expression, migration and invasion abilities and SOS1/MEK/ ERK/MMP2/MMP9 activation induced by TGF-β stimulation in 786-O cells could be antagonized by miR-429 overexpression. Exogenous re-expression of CRKL abrogated miR-429 suppression on the migration and invasion of 786-O cells. Collectively, miR-429 deficiency negatively correlated with CRKL overexpression promoted the aggressiveness of cancer cells and advanced the clinical progression of ccRCC patients. miR-429-CRKL axial regulation provides new clues to the fundamental research, diagnosis and treatment of ccRCC.
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http://dx.doi.org/10.1016/j.biopha.2020.110215DOI Listing
July 2020

GRIM-19 deficiency promotes clear cell renal cell carcinoma progression and is associated with high TNM stage and Fuhrman grade.

Oncol Lett 2020 Jun 31;19(6):4115-4121. Epub 2020 Mar 31.

College of Basic Medicinal Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.

Clear cell renal cell carcinoma (ccRCC) exhibits the highest mortality among all urological malignancies. The investigation of the potential disease progression markers can improve ccRCC diagnosis and treatment. Gene associated with retinoid-interferon-induced mortality-19 (GRIM-19) is involved in carcinogenesis and cancer progression in a variety of cancer types including RCC. While, its role in ccRCC remains unclear, this cancer type is considered the most aggressive RCC subtype. In the present study, RT-qPCR, western blotting and immunohistochemical (IHC) assays demonstrated that GRIM-19 protein and mRNA levels were downregulated in ccRCC tumor tissues compared with the corresponding levels noted in paracancerous non-tumor tissues. The deficiency of this protein contributed in relaxed and/or collapsed structures of the kidney tubules and collecting duct noted in tumor tissues. Moreover, the reduction in GRIM-19 expression was associated with high tumor, lymph nodes and metastasis (TNM) stage and Fuhrman grade of ccRCC tumors. The data suggested that GRIM-19 acted as a tumor suppressor and that its deficiency promoted ccRCC development and progression. GRIM-19 can be considered a potential tumor marker for ccRCC.
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http://dx.doi.org/10.3892/ol.2020.11498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202299PMC
June 2020

Erratum to: Smad4 mediates malignant behaviors of human ovarian carcinoma cell through the effect on expressions of E-cadherin, plasminogen activator inhibitor-1 and VEGF.

BMB Rep 2020 04;53(4):240

Key Laboratory for Proteomics of Liaoning Province, Dalian Medical University, Dalian University, Dalian 116044, China.

[Erratum to: BMB Reports 2010; 43(8): 554-560, PMID: 20797318] The authors apologize that due to our neglect when doing the picture layout of Fig. 1A, the wrong Western blot analysis image were pasted for the "β-actin"group in the middle plot of Fig. 1A. The middle plot of Fig. 1A and its related statistics results (bottom plot in Fig.1A) have been corrected. However, the conclusions of the original article are not affected. The authors would like to apologize for any inconvenience caused.
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April 2020

A novel ETV6-miR-429-CRKL regulatory circuitry contributes to aggressiveness of hepatocellular carcinoma.

J Exp Clin Cancer Res 2020 Apr 23;39(1):70. Epub 2020 Apr 23.

Department of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, China.

Background: Tumor metastasis is one of the main causes of the high mortality of hepatocellular carcinoma (HCC). E-Twenty Six variant gene 6 (ETV6) is a strong transcriptional repressor, associated with the development and progression of tumors. However, the exact role and underlying mechanism of ETV6 in HCC remain unclear.

Methods: Western blotting, quantitative real-time PCR and immunohistochemistry were used to detect the expression levels of ETV6, CRKL (v-crk sarcoma virus CT10 oncogene homologue (avian)-like) and miR-429 in HCC tissues and cells; Transwell chamber and F-actin cytoskeleton staining assay to examine the effects of ETV6 and CRKL deregulation on the migration, invasion and cytoskeleton of HCC cells; Co-immunoprecipitation assay to determine the interaction between CRKL and ETV6; Chromatin immunoprecipitation assay to investigate the interaction between ETV6 and miR-429.

Results: We established a novel ETV6-miR-429-CRKL regulatory circuitry contributes to HCC metastasis. ETV6 and CRKL were frequently increased, while miR-429 was downregulated in both hepatocarcinoma tissues and hepatocarcinoma cells. Moreover, ETV6 upregulation was positively correlated with CRKL upregulation, and two negative correlations were also established for ETV6 and CRKL upregulation with miR-429 downregulation in both hepatocarcinoma patients' tumorous tissues and hepatocarcinoma cells. Functional investigations revealed that overexpression and knockdown of ETV6 was remarkably effective in promoting and suppressing HCC cell migration, invasion, cytoskeleton F-actin expression and arrangement, whereas, CRKL overexpression exhibited similar effects to the overexpression of ETV6. Mechanistically, ETV6 negatively regulates miR-429 expression by directly binding to the promoter region of miR-429; miR-429 negatively regulates CRKL expression by selectively targeting CRKL-3'-UTR; ETV6 directly binds to CRKL and positively regulates its expression, which in turn CRKL positively regulates ETV6 expression.

Conclusions: Our data demonstrated that ETV6 promotes migration and invasion of HCC cells by directly binding to promoter region of miR-429 via modulating CRKL expression. The newly identified ETV6-miR-429-CRKL regulatory circuitry contributes to the aggressiveness of HCC, which provides new clues for fundamental research on diagnosis and treatment parameters for HCC.
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http://dx.doi.org/10.1186/s13046-020-01559-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178969PMC
April 2020

Bidirectional interaction of lncRNA AFAP1-AS1 and CRKL accelerates the proliferative and metastatic abilities of hepatocarcinoma cells.

J Adv Res 2020 Jul 30;24:121-130. Epub 2020 Mar 30.

Department of Biochemistry, College of Basic Medical Sciences, Dalian Medical University, 9 West Section, Lvshun Southern Road, Dalian, Liaoning 116044, China.

Actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1), a long non-coding RNA transcribed from the antisense strand of protein coding gene AFAP1, has attracted attention in cancer research. Despite, its biological function and regulatory mechanism in hepatocellular carcinoma still unknown. The present study revealed AFAP1-AS1 mediated hepatocarcinoma progression through targeting CRKL. The bidirectional interaction of AFAP1-AS1 and oncogenic protein CRKL, and the deregulation of AFAP1-AS1 effects on Ras, MEK and c-Jun activities were investigated in depth. AFAP1-AS1 was upregulated in surgical tumorous tissues from hepatocarcinoma patients compared with the paired paracancerous non-tumor liver tissues, and in hepatocarcinoma Huh7, HCCLM3 and HepG2 cell lines compared with LO2, a normal liver cell line. AFAP1-AS1 knockdown noticeably suppressed the proliferative, migratory and invasive properties, and the epithelial-mesenchymal transition (EMT) process of HepG2 and HCCLM3 through upregulating E-cadherin and downregulating N-cadherin and vimentin. CRKL knockdown reduced AFAP1-AS1 expression levels in HepG2 and HCCLM3 cells. AFAP1-AS1 suppression impaired CRKL expression in HepG2 and HCCLM3. AFAP1-AS1 level change was positively correlated with the expression level changes of Ras, MEK and c-Jun in mediating the invasiveness of hepatocarcinoma cells. Current work demonstrated AFAP1-AS1 to be an applicable progression indicator of hepatocarcinoma. AFAP1-AS1 probably promotes the proliferation, EMT progression and metastasis of hepatocarcinoma cells CRKL mediated Ras/MEK/c-Jun and cadherin/vimentin signaling pathways. AFAP1-AS1-CRKL bidirectional feedback signaling is worthy of further study on the monitoring, diagnosis and treatment of cancers.
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http://dx.doi.org/10.1016/j.jare.2020.03.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139140PMC
July 2020

CRKII overexpression promotes the proliferation, migration and invasion potential of murine hepatocarcinoma Hca-P cells.

Oncol Lett 2019 Jun 27;17(6):5169-5174. Epub 2019 Mar 27.

Department of Biochemistry, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.

Lymphatic metastasis is a major mechanism of tumor metastasis. The present study aimed to investigate the association of CRKII, a member of the CRK family, with the malignant behaviors of a murine hepatocarcinoma Hca-P cell line, with a lymph node metastatic rate of ~25%. Total mRNA was extracted from Hca-P cells, and then the murine CRKII gene was amplified by polymerase chain reaction and cloned into the pEASY-blunt cloning vector. Subsequently, the recombinant pcDNA3.1/V5-HisB-CRKII plasmid was constructed and transfected into Hca-P cells. Western blotting indicated that the CRKII expression level in pcDNA3.1/V5-HisB-CRKII-Hca-P cells was increased by ~185%, compared with pcDNA3.1/V5-HisB-Hca-P cells. The stable overexpression of CRKII enhanced the proliferation ability, as measured with a Cell Counting Kit-8 assay, and the colony forming capacity was measured with a soft agar colony forming assay for Hca-P cells. The migration and invasion capacities of Hca-P cells were increased by ~179 and 156% in Hca-P cells, respectively, following the stable upregulation of CRKII. Collectively, the recombinant pcDNA3.1/V5-HisB-CRKII-Hca-P plasmid was constructed successfully. Additionally, the CRKII expression level was positively associated with the proliferation, migration and invasion malignant properties of Hca-P cells.
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http://dx.doi.org/10.3892/ol.2019.10194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507350PMC
June 2019

miR-4521-FAM129A axial regulation on ccRCC progression through TIMP-1/MMP2/MMP9 and MDM2/p53/Bcl2/Bax pathways.

Cell Death Discov 2019 15;5:89. Epub 2019 Apr 15.

1Department of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, 116044 Dalian, China.

Clear cell renal cell carcinoma (ccRCC) is the most aggressive RCC subtype with high metastasis, chemotherapy and radiotherapy resistance, and poor prognosis. This study attempted to establish the deregulations of miR-4521 and FAM129A together with their correlation to and mechanism of regulation of ccRCC development and progression. FAM129A acted as tumor promotor and miR-4521 acted as a suppressor in ccRCC. As measured in surgical tumorous tissues from ccRCC patients, FAM129A overexpression and miR-4521 deficiency together contributed to ccRCC progression by promoting advances in patients' TNM stage and Fuhrman grade. Both the FAM129A knockdown and miR-4521 overexpression could reduce the in vitro migration and invasion abilities of renal cancer cells 786-O and ACHN, through the TIMP-1/MMP2/MMP9 pathway and could decrease their proliferation by promoting their apoptosis through the MDM2/p53/Bcl2/Bax pathway. By directly targeting the 3'-UTR domain of , miR-4521 was negatively correlated with /FAM129A levels in ccRCC progression and renal cancer cell malignancies. This work establishes the miR-4521-FAM129A axial regulation mechanism in ccRCC. Micro-4521 deficiency leads to /FAM129A upregulation, which synergistically enhances the migration and invasion of renal cancer cells due to the induced decrease of TIMP-1 and increases of MMP2 and MMP9, and increases their growth through escaping apoptosis by suppressing p53 by way of upregulation of induced MDM2. The current work provides new clues to assist fundamental research into the diagnosis and treatment of ccRCC.
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http://dx.doi.org/10.1038/s41420-019-0167-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465337PMC
April 2019

Annexin A5 regulates hepatocarcinoma malignancy via CRKI/II-DOCK180-RAC1 integrin and MEK-ERK pathways.

Cell Death Dis 2018 05 25;9(6):637. Epub 2018 May 25.

Department of Biotechnology, Dalian Medical University, 9 West Section, Lvshun Southern Road, Dalian, 116044, China.

As a calcium-dependent phospholipid binding annexin protein, annexin A5 (Anxa5) links to the progression, metastasis, survival, and prognosis of a variety of cancers. Current work showed ANXA5 overexpression was positively correlated with the upregulations of CRKI/II and RAC1 in hepatocarcinoma (HCC) patients' tissues, which potentially enhanced the clinical progression and lymphatic metastasis of HCC. The role and action mechanism of ANXA5 in hepatocarcinoma was then investigated using a hepatocarcinoma Hca-P cell line, an ideal and well-established murine cell model with 100% inducible tumorigenicity of implanted mice with low (~25%) lymph node metastatic (LNM) rate. In vitro evidences indicated ANXA5 stable knockdown resulted in decreased proliferation, migration, invasion and adhesion to lymph node (LN), and increased intercellular cohesion behaviors of hepatocarcinoma Hca-P cells. Consistently, stable ANXA5 knockdown led to reduced in vivo tumorigenicity and malignancy, LNM rate and level potentials of Hca-P- transplanted mice via inhibiting CD34 and VEGF3. The levels of CRKI/II and RAC1 were reduced in tumor tissues from mice transplanted with Hca-P cells with stable ANXA5 knockdown. Molecular action investigation further showed ANXA5 downregulation apparently suppressed the expressions of molecules CRKI/II, DOCK180, RAC1 in integrin pathway, p-MEK, p-ERK, c-Myc, and MMP-9 in MEK- ERK pathway together with VIMINTIN in Hca-P cells in appropriate to knockdown extent. Collectively, Anxa5 was able to mediate HCC carcinogenesis via integrin and MEK-ERK pathways. It is of potential use in the research and treatment of HCC.
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http://dx.doi.org/10.1038/s41419-018-0685-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5970249PMC
May 2018

miR-429 suppresses tumor migration and invasion by targeting CRKL in hepatocellular carcinoma via inhibiting Raf/MEK/ERK pathway and epithelial-mesenchymal transition.

Sci Rep 2018 02 5;8(1):2375. Epub 2018 Feb 5.

Department of Biotechnology, Dalian Medical University, Dalian, Liaoning, 116044, China.

Tumor metastasis is one of the main causes of hepatocellular carcinoma (HCC) high mortality. CRKL (v-crk sarcoma virus CT10 oncogene homologue (avian)-like) play important roles in tumor metastasis, however, the exact role and underlying mechanism of CRKL in HCC is still unknown. In our study, we demonstrated miR-429 negatively regulated CRKL expression via selectively binding to CRKL-3'-UTR at 3728-3735 bp site by post-transcriptionally mediating its functionality. Re-expression and silencing of miR-429 was remarkably effective in suppressing and promoting HepG2 cell migration and invasion in vitro. Knockdown or overexpression of CRKL exhibited similar effects as the overexpression or silencing of miR-429, whereas, CRKL overexpression (without the 3'-UTR) abrogated miR-429-induced inhibition on HepG2 migration and invasion. Moreover, miR-429-CRKL axis affected HepG2 migration and invasion potentials by regulating the adhesion ability, cytoskeleton F-actin expression and arrangement of HepG2. Furthermore, interference of Raf/MEK/ERK pathway and EMT contributed to miR-429-CRKL axis mediated metastasis inhibition. Nevertheless, miR-429 could not inhibit HepG2 proliferation through CRKL/c-Jun pathway. Taken together, our data demonstrated that miR-429 might function as an antimetastatic miRNA to regulate HCC metastasis by directly targeting CRKL via modulating Raf/MEK/ERK-EMT pathway. The newly identified miR-429-CRKL axis represents a novel potential therapeutic target for HCC treatment.
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http://dx.doi.org/10.1038/s41598-018-20258-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5799248PMC
February 2018

Serum fetuin-A levels in obese and non-obese subjects with and without type 2 diabetes mellitus.

Clin Chim Acta 2018 Jan 22;476:98-102. Epub 2017 Nov 22.

Department of endocrinology, Affiliated Yancheng Hospital, School of Medicine, Southeast University, Yancheng, Jiangsu 224001, PR China.

Background: Higher fetuin-A expression is linked to both obesity and type 2 diabetes mellitus (T2DM), However, studies in non-obese patients with T2DM are scarce.

Methods: 345 newly diagnosed T2DM patients and 300 subjects with normal glucose tolerance (NGT) were divided into obese and non-obese subgroups, respectively. Serum fetuin-A and adiponectin levels and related parameters were measured.

Results: T2DM patients with obesity had higher fetuin-A levels compared with non-obese patients and obese NGT subjects (p<0.001). Significant correlations were observed between fetuin-A and most metabolic parameters in obese NGT and T2DM subjects, but which was not in non-obese patients with T2DM. The independent associations were found between fetuin-A and free fatty acids, HOMA-IR, C-reactive protein and adiponectin only in obese NGT and T2DM subjects (all p<0.05). The adjusted odds ratios for obesity were increased with increasing quartile of fetuin-A in both T2DM and NGT subjects in logistic regression models (p for trend<0.001), but which was more significant in T2DM patients.

Conclusion: Higher serum fetuin-A levels in obese T2DM patients compared with non-obese patients and obese NGT subjects supports the hypothesis that fetuin-A may be as a bridge connecting obesity and obesity-related T2DM.
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http://dx.doi.org/10.1016/j.cca.2017.11.023DOI Listing
January 2018

Anxa5 mediates the in vitro malignant behaviours of murine hepatocarcinoma Hca-F cells with high lymph node metastasis potential preferentially via ERK2/p-ERK2/c-Jun/p-c-Jun(Ser73) and E-cadherin.

Biomed Pharmacother 2016 Dec 30;84:645-654. Epub 2016 Sep 30.

Department of Biotechnology, Dalian Medical University, Dalian 116044, China. Electronic address:

Objective: Annexin A5 (Anxa5) is associated with the progression of some cancers, while its role and regulation mechanism in tumor lymphatic metastasis is rarely reported. This study aims to investigate the influence of Anxa5 knockdown on the malignant behaviours of murine hepatocarcinoma Hca-F cell line with high lymph node metastatic (LNM) potential and the underlying regulation mechanism.

Methods: RNA interfering was performed to silence Anxa5 in Hca-F. Monoclonal shRNA-Anxa5- Hca-F cells were obtained via G418 screening by limited dilution method. Quantitative real-time RT-PCR (qRT-PCR) and Western blotting (WB) were applied to measure Anxa5 expression levels. CCK-8, Boyden transwell-chamber and in situ LN adhesion assays were performed to explore the effects of Anxa5 on the proliferation, migration, invasion and adhesion capacities of Hca-F. WB and qRT-PCR were used to detect the level changes of key molecules in corresponding signal pathways.

Results: We obtained two monoclonal shRNA-Anxa5-transfected Hca-F cell lines with stable knockdowns of Anxa5. Anxa5 knockdown resulted in significantly reduced proliferation, migration, invasion and in situ LN adhesion potentials of Hca-F in proportion to its knockdown extent. Anxa5 downregulation enhanced E-cadherin levels in Hca-F. Moreover, Anxa5 affected Hca-F behaviours specifically via ERK2/p-ERK2/c-Jun/p-c-Jun(Ser73) instead of p38MAPK/c-Jun, Jnk/c-Jun and AKT/c-Jun pathways.

Conclusions: Anxa5 mediates the in vitro malignant behaviours of murine hepatocarcinoma Hca-F cells via ERK2/c-Jun/p-c-Jun(Ser73) and ERK2/E-cadherin pathways. It is an important molecule in metastasis (especially LNM) and a potential therapeutic target for hepatocarcinoma.
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http://dx.doi.org/10.1016/j.biopha.2016.09.086DOI Listing
December 2016

ANXA11 regulates the tumorigenesis, lymph node metastasis and 5-fluorouracil sensitivity of murine hepatocarcinoma Hca-P cells by targeting c-Jun.

Oncotarget 2016 Mar;7(13):16297-310

Department of Biotechnology, Dalian Medical University, Dalian 116044, China.

Annexin A11 (Anxa11) is associated with various cancers. Using a pair of syngeneic murine hepatocarcinoma cells, Hca-P with ~25% and Hca-F with ~75% lymph node metastatic (LNM) potentials, we demonstrated Anxa11 involvement in hepatocarcinoma lymphatic metastasis. Here, ANXA11 acted as a suppressor for the tumorigenicity, LNM and 5-FU resistance of Hca-P via c-Jun. We constructed monoclonal Hca-P cell line with stable ANXA11 knockdown. Although Bax and Bcl-2 levels increased in shRNA-Anxa11-transfected Hca-P, ANXA11 downregulation showed no clear effect on Hca-P apoptosis. ANXA11 downregulation promoted in vitro migration and invasion capacities of Hca-P. In situ adhesion potential of Hca-P cells toward LN was significantly enhanced following ANXA11 downregulation. Consistently, ANXA11 downregulation promoted the in vivo tumor growth and LNM capacities of Hca-P cells. ANXA11 knockdown enhanced the chemoresistance of Hca-P cells specifically toward 5-FU instead of cisplatin. Its downregulation increased c-Jun (pSer73) and decreased c-Jun (pSer243) levels in Hca-P. c-Jun (pSer243) downregulation seemed to be only correlated with ANXA11 knockdown without the connection to 5-FU treatment. Interestingly, compared with scramble-Hca-P cells, the levels of c-Jun and c-Jun (pSer73) in shRNA-Anxa11-Hca-P cells were upregulated in the presences of 0.1 and 1.0 mg/L 5-FU. The levels changes from c-Jun and c-Jun (pSer73) in Hca-P cells showed a more obvious tendency with the combination of ANXA11 knockdown and 5-FU treatment. ANXA11 level regulates LNM and 5-FU resistance of Hca-P via c-Jun pathway. It might play an important role in hepatocarcinoma cell malignancy and be a therapeutic target for hepatocarcinoma.
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http://dx.doi.org/10.18632/oncotarget.7484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941315PMC
March 2016

Serum fetuin-A levels are independently correlated with vascular endothelial growth factor and C-reactive protein concentrations in type 2 diabetic patients with diabetic retinopathy.

Clin Chim Acta 2016 Apr 4;455:113-7. Epub 2016 Feb 4.

Department of Endocrinology, Affiliated Yancheng Hospital, School of Medicine, Southeast University, Yancheng, Jiangsu 224001, PR China.

Background: The higher expression of vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) is associated with the development of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM). Fetuin-A is shown to have proangiogenic and proinflammatory effects.

Methods: This study included 245 T2DM patients consisting of 95 cases with non-diabetic retinopathy (NDR), 78 cases with non-proliferative diabetic retinopathy (NPDR) and 72 cases with proliferative diabetic retinopathy (PDR), in addition to 65 healthy controls. Serum fetuin-A, VEGF and CRP concentrations and related parameters were measured.

Results: Significant positive correlations were found between fetuin-A and VEGF and CRP, and between VEGF and CRP in T2DM patients (all p<0.001). After adjustment for confounders, fetuin-A was correlated independently with VEGF and CRP in NPDR and PDR patients, but not in NDR subjects. In addition, fetuin-A was correlated independently with HOMA-IR (all 4 groups), HbA1c (NDR, NPDR and PDR groups) and duration of diabetes (PDR group). When compared with NDR and control subjects, NPDR and PDR patients had higher HOMA-IR.

Conclusions: Serum fetuin-A concentrations are independently correlated with VEGF and CRP concentrations in T2DM patients with DR, but not in NDR subjects.
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http://dx.doi.org/10.1016/j.cca.2016.02.003DOI Listing
April 2016

Value of serum marker HE4 in pulmonary carcinoma diagnosis.

Int J Clin Exp Med 2015 15;8(10):19014-21. Epub 2015 Oct 15.

Department of Clinical Laboratory, Affiliated Yancheng Hospital, School of Medicine, Southeast University Yancheng 224001, Jiangsu Province, P. R. China.

An effective blood test is valuable to aid clinicians in making case management decisions. The present study was to analyze the value of four serum tumor markers for the diagnosis of pulmonary carcinoma. The case group consisted of 80 pulmonary carcinoma patients, which were compared to a control group of 30 patients with benign pulmonary disease and a control group of 30 healthy individuals. Serum levels of carcinoma embryonic antigen (CEA), cytokeratin protein fragment 21-1 (CYFRA21-1), neuron-specific enolase (NSE), and human epididymis protein 4 (HE4) were detected using electrochemiluminescence. Serum CEA, NSE, CYFRA21-1, and HE4 levels were significantly higher in pulmonary carcinoma patients than those in both control groups (P < 0.05). Serum CEA and HE4 levels were significantly higher in adenocarcinoma patients, while serum CYFRA21-1 levels were significantly higher in squamous cell carcinoma patients and serum NSE levels were significantly higher in small cell lung cancer (SCLC) patients (P < 0.05). Analysis of area-under-the-receiver operating characteristic (ROC) curves (AUC) revealed that serum CYFRA21-1, CEA, and HE4 levels were valuable for squamous cell carcinoma, serum CEA and HE4 levels were valuable for adenocarcinoma, and serum NSE level was valuable for SCLC (P < 0.05). Serum CEA and HE4 levels of pulmonary carcinoma patients with metastasis were higher than those with TNM stage I-II or III-IV disease without metastasis. In brief, detection of serum HE4 levels may be useful in auxiliary diagnosis and evaluation of the progression of pulmonary carcinoma.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694427PMC
January 2016

Akbu-LAAO exhibits potent anti-tumor activity to HepG2 cells partially through produced H2O2 via TGF-β signal pathway.

Sci Rep 2015 Dec 14;5:18215. Epub 2015 Dec 14.

Department of Biotechnology, Dalian Medical University, Dalian, Liaoning, 116044, China.

Previously, we characterized the biological properties of Akbu-LAAO, a novel L-amino acid oxidase from Agkistrodon blomhoffii ussurensis snake venom (SV). Current work investigated its in vitro anti-tumor activity and underlying mechanism on HepG2 cells. Akbu-LAAO inhibited HepG2 growth time and dose-dependently with an IC50 of ~38.82 μg/mL. It could induce the apoptosis of HepG2 cells. Akbu-LAAO exhibited cytotoxicity by inhibiting growth and inducing apoptosis of HepG2 as it showed no effect on its cell cycle. The inhibition of Akbu-LAAO to HepG2 growth partially relied on enzymatic-released H2O2 as catalase only partially antagonized this effect. cDNA microarray results indicated TGF-β signaling pathway was linked to the cytotoxicity of Akbu-LAAO on HepG2. TGF-β pathway related molecules CYR61, p53, GDF15, TOB1, BTG2, BMP2, BMP6, SMAD9, JUN, JUNB, LOX, CCND1, CDK6, GADD45A, CDKN1A were deregulated in HepG2 following Akbu-LAAO stimulation. The presence of catalase only slightly restored the mRNA changes induced by Akbu-LAAO for differentially expressed genes. Meanwhile, LDN-193189, a TGF-β pathway inhibitor reduced Akbu-LAAO cytotoxicity on HepG2. Collectively, we reported, for the first time, SV-LAAO showed anti-tumor cell activity via TGF-β pathway. It provides new insight of SV-LAAO exhibiting anti-tumor effect via a novel signaling pathway.
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http://dx.doi.org/10.1038/srep18215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4677388PMC
December 2015

Role of annexin A6 in cancer.

Oncol Lett 2015 Oct 15;10(4):1947-1952. Epub 2015 Jul 15.

Department of Biotechnology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.

Annexin A6 (AnxA6) is a member of a conserved superfamily of Ca-dependent membrane-binding annexin proteins. It participates in membrane and cytoskeleton organization, cholesterol homeostasis, membrane trafficking, cell adhesion and signal transduction. The expression levels of AnxA6 are closely associated with melanoma, cervical cancer, epithelial carcinoma, breast cancer, gastric cancer, prostate cancer, acute lymphoblastic leukemia, chronic myeloid leukemia, large-cell lymphoma and myeloma. AnxA6 exhibits dual functions in cancer, acting either as a tumor suppressor or promoter, depending on the type of cancer and the degree of malignancy. In several types of cancer, AnxA6 acts via Ras, Ras/MAPK and/or FAK/PI3K signaling pathways by mainly mediating PKCα, p120GAP, Bcr-Abl and YY1. In the present review, the roles of AnxA6 in different types of cancer are summarized.
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http://dx.doi.org/10.3892/ol.2015.3498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579822PMC
October 2015

ANXA5 level is linked to in vitro and in vivo tumor malignancy and lymphatic metastasis of murine hepatocarcinoma cell.

Future Oncol 2016 Jan 30;12(1):31-42. Epub 2015 Nov 30.

Department of Biotechnology, Dalian Medical University, 9 West Section, Lvshun Southern Road, Dalian 116044, China.

Aim: To investigate ANXA5 overexpression on in vitro and in vivo malignancies of murine Hca-P cells.

Materials & Methods: Hca-P with low lymph node metastasis (LNM) potential was used as cell model. TEM, CCK-8 and Boyden transwell assays were performed for in vitro Hca-P behaviors. Hca-P-transplanted mouse model was established for in vivo experiment.

Results: ANXA5-overexpressing monoclonal Anxa5-Hca-P-1, Anxa5-Hca-P-2 and Anxa5-Hca-P-3 cells were obtained. ANXA5 upregulation alters the proliferation, morphology and rough endoplasmic reticulum of Hca-P cells, enhances in vitro migration and invasions of Hca-P, promotes in vivo malignant degree and LNM rate of Anxa5-Hca-P-3-transplanted mice.

Conclusion: As a potential indicator for malignancy and lymphatic metastasis, ANXA5 overexpression increases in vitro migration and invasion of Hca-P cell, promotes in vivo malignancy, LNM rate and level of Hca-P-transplanted mice.
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http://dx.doi.org/10.2217/fon.15.289DOI Listing
January 2016

rAdinbitor, a disintegrin from Agkistrodon halys brevicaudus stejneger, inhibits tumorigenicity of hepatocarcinoma via enhanced anti-angiogenesis and immunocompetence.

Biochimie 2015 Sep 29;116:34-42. Epub 2015 Jun 29.

Department of Biotechnology, Dalian Medical University, Dalian, 116044, China; Liaoning Provincial Core Lab of Cell and Molecular Biology, Dalian Medical University, Dalian 116044, China. Electronic address:

Adinbitor is a disintegrin previously obtained from Agkistrodon halys brevicaudus stejneger by our group. Here, we investigated the in vitro and in vivo anti-tumor activities of recombinant Adinbitor (rAdinbitor). rAdinbitor stimulation can inhibit the in vitro proliferation, migration and invasion capacities of murine hepatocarcinoma H22 and Hca-F cells. The administrations of rAdinbitor either by gavage or intraperitoneal injection suppress the tumor malignancy and prolong the survival rate and time of H22-transplanted mice. The number and size of formed blood vessels decreased dramatically in tumorous tissues in that the expression levels of vascular endothelial growth factor (VEGF) and cluster of differentiation 34 (CD34) were significantly decreased in responding to rAdinbitor treatment. The protein levels of IL-18 and IgG increased significantly in the serum of H22-transplanted tumor mice with rAdinbitor treatment. rAdinbitor shows in vitro and in vivo anti-tumor effects as an angiogenesis inhibitor and immunocompetence enhancer.
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http://dx.doi.org/10.1016/j.biochi.2015.06.026DOI Listing
September 2015

Annexin A4 and cancer.

Clin Chim Acta 2015 Jul 3;447:72-8. Epub 2015 Jun 3.

Department of Biotechnology, Dalian Medical University, Dalian 116044, China. Electronic address:

Annexin A4 (Anxa4) is one of the Ca(2+)-regulated and phospholipid-binding annexin superfamily proteins. Anxa4 has a potential role in diagnosis, prognosis, and treatment of certain cancers. Studies indicate that Anxa4 up-regulation promotes the progression of tumor and chemoresistance of colorectal cancer (CRC), esophageal squamous cell carcinoma (ESCC), endometrial carcinoma (EC), gastric cancer (GC), chemoresistant lung cancer (LC), malignant mesothelioma (MM), renal cell carcinoma (RCC), ovarian clear cell carcinoma (OCCC), cholangiocarcinoma, hepatocellular carcinoma (HCC), breast cancer (BC), and laryngeal cancer. Interestingly, Anxa4 also might specifically function as a tumor suppressor for prostate cancer (PCa) and have a paradoxical role for pancreatic cancer (PCC). Differential expression of Anxa4 may distinguish major salivary gland tumor (MSGT) from thyroid cancer. In addition, its differential expression was linked to Sirt1-induced cisplatin resistance of oral squamous cell carcinoma (OSCC) and miR-7-induced migration and invasion inhibition of glioma. This current review summarizes and discusses the clinical significance of Anxa4 in cancer as well as its potential mechanisms of action. It may provide new integrative understanding for future studies on the exact role of Anxa4 in cancer.
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http://dx.doi.org/10.1016/j.cca.2015.05.016DOI Listing
July 2015

CRKL knockdown promotes in vitro proliferation, migration and invasion, in vivo tumor malignancy and lymph node metastasis of murine hepatocarcinoma Hca-P cells.

Biomed Pharmacother 2015 Apr 26;71:84-90. Epub 2015 Feb 26.

Department of Biochemistry, Dalian Medical University, Dalian 116044, China; Provincial Key Laboratory of Cell and Molecular Biology, Dalian Medical University, Dalian 116044, China. Electronic address:

Our previous study (Biomed Pharmacother 2015;69:11) demonstrated that the over-expression of CRKL, a chicken tumor virus number 10 regulator of kinase-like protein, suppresses in vitro proliferation, invasion and migration of murine hepatocarcinoma Hca-P cell, a murine HCC cell with lymph node metastatic (LNM) rate of ∼25%. In current work, we investigated the effects of CRKL knockdown on the in vitro cell proliferation, migration and invasion, and on the in vivo tumor malignancy and LNM rate and level for Hca-P cells. Western blotting assay indicated that CRKL was down-regulated by ∼90% in a monoclonal CrkL-shRNA-transfected Hca-P cells. Compared with Hca-P and unrelated-shRNA-transfected Hca-P cell, the in vitro proliferation, migration and invasion potentials were significantly enhanced following CRKL stable deregulation. CRKL knock-down significantly promoted the tumorigenicity malignancy, LNM rates and level of Hca-P-transplanted mice. Consistent with our previous work, it can be concluded CRKL plays an important role in hepatocarcinoma cell proliferation, invasion and migration as well hepatocarcinoma malignancy and metastasis. It functions as a potential tumor suppressor in hepatocarcinoma.
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http://dx.doi.org/10.1016/j.biopha.2015.02.022DOI Listing
April 2015

Annexin A11 knockdown inhibits in vitro proliferation and enhances survival of Hca-F cell via Akt2/FoxO1 pathway and MMP-9 expression.

Biomed Pharmacother 2015 Mar 12;70:58-63. Epub 2015 Jan 12.

Department of Biotechnology, Dalian Medical University, Dalian 116044, China. Electronic address:

Annexin A11 (Anxa11), a Ca(2+)-regulated phospholipid-binding protein, is involved in cell apoptosis, differentiation, vesicle trafficking, cancer progression and autoimmune diseases. Previous study from our group indicated that Anxa11 was associated with lymphatic metastatic potential of murine hepatocarcinoma cells. Herein, we investigated the effects and action mechanism of Anxa11 knockdown on in vitro cell proliferation and apoptosis of Hca-F, a murine hepatocarcinoma cell with∼75% lymph node metastatic potential. Real-time PCR and western blotting assays indicated that Anxa11 was significantly downregulated in monoclonal Anxa11-shRNA-transfected Hca-F cells. Anxa11 knockdown in Hca-F suppressed its in vitro proliferation and cell apoptosis capacities. Following Anxa11 knockdown in Hca-F cells, Bax/Bcl-2 expression level ratio, Akt2 and FoxO1 (pSer319) expression levels as well as MMP-9 mRNA and active MMP-9 protein levels were significantly elevated in Hca-F cells. In conclusion, Annexin A11 knockdown inhibits the in vitro proliferation and cell apoptosis of Hca-F cell via Akt2/FoxO1 and/or MMP-9 expression pathway. Anxa11 might play an important role in hepatocarcinoma cell invasion and metastasis and hepatocarcinoma malignancy.
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http://dx.doi.org/10.1016/j.biopha.2015.01.011DOI Listing
March 2015

CRKL overexpression suppresses in vitro proliferation, invasion and migration of murine hepatocarcinoma Hca-P cells.

Biomed Pharmacother 2015 Feb 4;69:11-7. Epub 2014 Nov 4.

Department of Biochemistry, Dalian Medical University, 116044 Dalian, PR China; Provincial Key Laboratory of Cell and Molecular Biology, Dalian Medical University, 116044 Dalian, PR China. Electronic address:

The signal adaptor CRK family protein play important roles in cancer cell progression, proliferation, migration and invasion. Previously, we showed that CRK was involved in lymphatic metastatic potential of murine hepatocarcinoma cells. In current work, as a member of CRK family, chicken tumour virus number 10 regulator of kinase-like protein (CRKL) was revealed to be associated with malignant behaviors of Hca-P, a murine HCC cell with lymph node metastatic (LNM) rate of ∼25%. CRKL overexpression in Hca-P by a constructed eukaryotic expression vector of pcDNA3.1/V5-HisB-CRKL significantly ameliorated its malignant biological properties. CCK-8 and soft agar colony formation assays indicated CRKL overexpression significantly inhibits the cell proliferation and colony formation abilities of Hca-P. Additionally, transwell assays indicated that the Hca-P cell migration and invasion capacities were apparently reduced following CRKL overexpression. As Hca-P is an ideal hepatocarcinoma cell model with low (initial) LNM potential, CRKL is shown to act as a potential suppressor and to provide new insight for both the malignant behaviors of hepatocarcinoma cells and lymphatic metastasis mechanism of hepatocarcinoma.
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http://dx.doi.org/10.1016/j.biopha.2014.10.025DOI Listing
February 2015

Genetic variants of the DNA damage repair genes XRCC4 and RAD51 are associated with susceptibility to esophageal cancer.

Clin Res Hepatol Gastroenterol 2015 Jun 19;39(3):379-83. Epub 2015 Jan 19.

Department of Clinical Laboratory, Affiliated Yancheng Hospital, School of Medicine, Southeast University, Yancheng 224001, Jiangsu Province, PR China.

Objective: Altered DNA damage repair genes have been demonstrated to contribute to tumorigenesis. This study explored the relationship of genetic polymorphisms of the DNA repair genes XRCC4 and RAD51 to the risk of esophageal cancer.

Methodology: Genotyping of XRCC4 G-1394T (rs6869366) and RAD51-G135C by PCR-RFLP analysis was performed on 477 participants, of whom 219 were patients with esophageal cancer; the remaining participants were healthy. Statistical analysis, including Chi(2) test and logistic regression, was used to assess genotypic distributions and their correlation with cancer risk.

Results: Carriers of the XRCC4 rs6869366 G allele (GT+GG) were at a significantly higher risk of esophageal cancer compared to individuals with the TT genotype [odds ratio (OR)=3.35, 95% confidence interval (CI): (1.16-10.24)]. Carriers of the C allele of RAD51 G135C (GC+CC) had a significantly increased risk of esophageal cancer compared to individuals with the GG genotype (OR=2.53, 95%CI: 1.15-6.70). Further, the variant genotypes of XRCC4 and RAD51 interacted to exacerbate the risk of esophageal cancer (OR=8.92, 95%CI: 2.47-38.20).

Conclusions: Variants of the DNA damage repair genes XRCC4 and RAD51 increase the risk of esophageal cancer.
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http://dx.doi.org/10.1016/j.clinre.2014.12.002DOI Listing
June 2015

The role of CT10 regulation of kinase-like in cancer.

Future Oncol 2014 Dec;10(16):2687-97

Department of Biotechnology, Dalian Medical University, Dalian, China.

V-crk avian sarcoma virus CT10 oncogene homolog-like (CRKL) is a member of CRK family. It acts as an adaptor protein in intracellular signal transduction. CRKL has been reported overexpressed in a variety of cancers affecting the aggressive and malignant behaviors of cancer cells. CRKL seems to show a tumor-promotion role in gastric cancer, glioblastoma multiforme, hepatocellular carcinoma, bladder cancer, lung cancer, colon cancer, ovarian cancer, leukemia, breast cancer, head and neck cancer, rhabdomyosarcoma and neuroblastoma. The association of CRKL with malignant tumors and its potential action mechanisms were summarized. CRKL has the potential to be used as a biomarker for the diagnosis, treatment and prognosis of certain tumors.
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http://dx.doi.org/10.2217/fon.14.199DOI Listing
December 2014

Comparative binding affinities of flavonoid phytochemicals with bovine serum albumin.

Iran J Pharm Res 2014 ;13(3):1019-28

Department of Biotechnology, Dalian Medical University, Dalian,116044, China.

Dietary flavonoids show beneficial effects in the prevention of chronic diseases. However, flavonoid bioavailability is poor, probably due to their interaction with serum albumins. In the current work, the binding interactions of eight related flavonoids, sharing a similar core structure, with bovine serum albumin (BSA) were investigated by fluorescence spectroscopy. The binding affinities of the flavonoids with BSA were in the order hesperetin (KA=5.59 × 10(5))> quercetin (4.94 × 10(5)) > naringenin (3.04 × 10(5)) > isoquercitrin (4.66 × 10(4)) > icariin (3.60 × 10(4)) > rutin (1.65 × 10(4)) > hesperidin (2.50 × 10(3)) > naringin (8.70 × 10(2)). The associations of specific structural components of the flavonoids with their binding properties to BSA were also explored and hydrophobicity, functional group substituents, steric hindrance effects and the spatial arrangements of substituents seem to be the key factors for the affinities of flavonoids towards BSA. The results from the current work contribute to a better understanding of the transport of flavonoids in plasma and helping predict their physiological functions based on their intrinsic structures.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4177624PMC
October 2014