Publications by authors named "Wenjie Huang"

169 Publications

Targeting HIF-1α/NOTCH1 pathway eliminates CD44 cancer stem-like cell phenotypes, malignancy, and resistance to therapy in head and neck squamous cell carcinoma.

Oncogene 2022 Jan 10. Epub 2022 Jan 10.

Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing, China.

Poor prognosis of head and neck squamous cell carcinomas (HNSCCs) results from resistance to chemotherapy and radiotherapy. To uncover the drivers of HNSCC resistance, including stemness and hypoxia, in this study, we compared the gene expression between CD44 and CD44 HNSCC cells and assessed the correlation of CD44 and hypoxia-inducible factor 1α (HIF-1α) expression with mouse features and outcomes of patients with HNSCC. We combined the knockdown or activation of HIF-1α with in vitro and in vivo assays to evaluate effects on stemness and resistance of HNSCC cells. Analysis of clinical data showed that activation of HIF-1α in CD44 patients with HNSCC was correlated with worse prognosis. Functional assays showed that HIF-1α promoted stemness, resistance, and epithelial-mesenchymal transition in HNSCC CD44 cells. HIF-1α activated NOTCH1 signaling in HNSCC stem-like cells characterized by CD44 expression. Moreover, inhibition of these signaling proteins using shRNA or Evofosfamide (Evo) development for cancer treatment, reversed chemoresistance in vitro and in vivo. Taken together, our results indicated that targeting HIF-1α attenuated NOTCH1-induced stemness, which regulates responses to chemotherapy or radiotherapy and malignancy in CD44 HNSCCs. HIF-1α/NOTCH1 signaling may represent a target for HNSCC treatment.
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http://dx.doi.org/10.1038/s41388-021-02166-wDOI Listing
January 2022

Mechanism of carbendazim in treating pebrine disease of Bombyx mori based on GC/MS-based metabonomics.

Parasitol Res 2022 Jan 6;121(1):453-460. Epub 2022 Jan 6.

Sericulture and Agri-Food Research Institute, Guangdong Academy of Agricultural Sciences, No. 133 Dongguanzhuang Yiheng Road, Guangzhou, 510610, China.

Pebrine disease is caused by microporidia (Nosema bombycis) and is destructive to sericulture production. A carbendazim-based drug FangWeiLing (FWL) has a significant control effect on the disease, which is a successful example of drug treatment of microsporidia. In this study, the therapeutic effect and critical action time of FWL were investigated by silkworm rearing biological test. Besides, the hemolymph samples from silkworms in the control group, model group, and FWL group were analyzed by metabonomics based on gas chromatography-mass spectrometry (GC/MS). The results showed that FWL had a significant therapeutic effect on pebrine disease, and the critical action time was 24 ~ 48 h post inoculation. Forty-seven different metabolites related to pebrine disease were screened out, and correlated with starch and sucrose metabolism; aminoacyl-tRNA biosynthesis; arginine biosynthesis; glycine, serine, and threonine metabolism; and phenylalanine, tyrosine, and tryptophan biosynthesis. After pretreatment with FWL, the metabolites were all effectively regulated, indicating productive intervention. Principal component analysis (PCA) also showed that the overall metabolic profile of the FWL group tended toward the control group. Compared with the control group, 16 different metabolites were obtained from the hemolymph of B.mori in FWL group, mainly involving aminoacyl-tRNA biosynthesis and taurine and hypotaurine metabolism. It indicated that FWL had some effect on silkworm metabolism, which might be related to the decrease in cocoon quality. In conclusion, combined with the life cycle of N. bombycis, the mechanism of carbendazim in the treatment of pebrine disease can be fully revealed. Carbendazim can effectively reduce the destruction of amino acid metabolism and carbohydrate metabolism by N. Bombycis infection by inhibiting the proliferation of the meronts in silkworms, thus maintaining the normal physiological state of B. mori and achieve therapeutic effects. GC/MS-based metabonomics is a valuable and promising strategy to understand the disease mechanism and drug treatment of pebrine disease.
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http://dx.doi.org/10.1007/s00436-021-07394-3DOI Listing
January 2022

Correction to: ONECUT2 facilitates hepatocellular carcinoma metastasis by transcriptionally upregulating FGF2 and ACLY.

Cell Death Dis 2021 Dec 23;13(1):28. Epub 2021 Dec 23.

Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.

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http://dx.doi.org/10.1038/s41419-021-04475-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8702544PMC
December 2021

A Pan-Cancer Analysis of the Oncogenic Role of Integrin Beta4 (ITGB4) in Human Tumors.

Int J Gen Med 2021 11;14:9629-9645. Epub 2021 Dec 11.

Department of Reproductive Medicine, Liuzhou Maternity and Child Healthcare Hospital, Affiliated Women and Children's Hospital of Guangxi University of Science and Technology, Liuzhou, Guangxi, 545001, People's Republic of China.

Background: Integrin beta4 (ITGB4) is a transmembrane receptor that plays a key role in tumorigenesis and tumor development. However, there are no pan-cancer analyses of ITGB4.

Methods: This study demonstrates the first potential oncogenic roles of ITGB4 across 33 tumors based on the dataset of the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO).

Results: ITGB4 is highly expressed in many cancers, and distinct correlations exist between ITGB4 expression and the prognosis of tumor patients. We also found that the methylation and genetic alteration level of ITGB4 was associated with some cancer prognosis. Furthermore, we found a reduced phosphorylation of ITGB4 at S1457 in several tumors, such as breast and ovarian cancers. Finally, ITGB4 expression was correlated with cancer-associated fibroblasts in liver hepatocellular carcinoma and prostate adenocarcinoma, and the infiltration level of NK cells and neutrophils was observed in other cancers, such as breast invasive carcinoma and lung adenocarcinoma. Moreover, RNA metabolism and protein processing-associated functions are involved in the functional mechanism of ITGB4.

Conclusion: Our first pan-cancer study may offer a relatively comprehensive understanding of the oncogenic roles of ITGB4 across different tumors.
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http://dx.doi.org/10.2147/IJGM.S341076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8674675PMC
December 2021

DNASE1L3 as a Novel Diagnostic and Prognostic Biomarker for Lung Adenocarcinoma Based on Data Mining.

Front Genet 2021 15;12:699242. Epub 2021 Nov 15.

Departments of Clinical Laboratory of Affiliated Liutie Central Hospital of Guangxi Medical University, Liuzhou, China.

Previous researches have highlighted that low-expressing deoxyribonuclease1-like 3 (DNASE1L3) may play a role as a potential prognostic biomarker in several cancers. However, the diagnosis and prognosis roles of DNASE1L3 gene in lung adenocarcinoma (LUAD) remain largely unknown. This research aimed to explore the diagnosis value, prognostic value, and potential oncogenic roles of DNASE1L3 in LUAD. We performed bioinformatics analysis on LUAD datasets downloaded from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus), and jointly analyzed with various online databases. We found that both the mRNA and protein levels of DNASE1L3 in patients with LUAD were noticeably lower than that in normal tissues. Low DNASE1L3 expression was significantly associated with higher pathological stages, T stages, and poor prognosis in LUAD cohorts. Multivariate analysis revealed that DNASE1L3 was an independent factor affecting overall survival (HR = 0.680, = 0.027). Moreover, decreased DNASE1L3 showed strong diagnostic efficiency for LUAD. Results indicated that the mRNA level of DNASE1L3 was positively correlated with the infiltration of various immune cells, immune checkpoints in LUAD, especially with some m6A methylation regulators. In addition, enrichment function analysis revealed that the co-expressed genes may participate in the process of intercellular signal transduction and transmission. GSEA indicated that DNASE1L3 was positively related to G protein-coupled receptor ligand biding (NES = 1.738; P adjust = 0.044; FDR = 0.033) and G alpha (i) signaling events (NES = 1.635; P adjust = 0.044; FDR = 0.033). Our results demonstrated that decreased DNASE1L3 may serve as a novel diagnostic and prognostic biomarker associating with immune infiltrates in lung adenocarcinoma.
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http://dx.doi.org/10.3389/fgene.2021.699242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8636112PMC
November 2021

Prognostic Value of Tumor Mutational Burden Related to Immune Infiltration in Cervical Squamous Cell Carcinoma.

Front Med (Lausanne) 2021 11;8:755657. Epub 2021 Nov 11.

Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

Cervical squamous cell carcinoma is one of the most common causes of female cancer deaths worldwide. At present, immunotherapy using immune checkpoint blockade (ICB) has improved the prognosis of many cancer patients, and neoantigens generated by mutations may serve as potential biomarkers for predicting the outcome of ICB therapy. In this study, we identified missense mutations as the most frequent in landscapes of gene mutation in cervical squamous cell carcinoma (CESC) samples. Patients with higher tumor mutation burden (TMB) presented higher overall survival (OS). In addition, there was a significant correlation between the high TMB group and fractions of most immune cells. Univariate and multivariate Cox regression analyses identified five hub genes (IFNG, SERPINA3, CCL4L2, TNFSF15, and IL1R1) that were used to build a prognostic model. In the prognostic model, the low-risk group achieved better OS. Mutations in the five hub genes mainly affected the infiltration level of CD8+ T cells and dendritic cells. In conclusion, our study is valuable for exploring the role of TMB and its relationship with immune infiltration in CESC. Moreover, the prognosis model may help predict the sensitivity of patients to immunotherapy and provide underlying biomarkers for personalized immunotherapy.
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http://dx.doi.org/10.3389/fmed.2021.755657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8631969PMC
November 2021

ONECUT2 facilitates hepatocellular carcinoma metastasis by transcriptionally upregulating FGF2 and ACLY.

Cell Death Dis 2021 11 27;12(12):1113. Epub 2021 Nov 27.

Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.

Metastasis is the predominant reason for high mortality of hepatocellular carcinoma (HCC) patients. It is critical to explore the molecular mechanism underlying HCC metastasis. Here, we reported that transcription factor One Cut homeobox 2 (ONECUT2) functioned as an oncogene to facilitate HCC metastasis. Elevated ONECUT2 expression was positively correlated with increased tumor number, tumor encapsulation loss, microvascular invasion, poor tumor differentiation, and advanced TNM stage. Mechanistically, ONECUT2 directly bound to the promoters of fibroblast growth factor 2 (FGF2) and ATP citrate lyase (ACLY) and transcriptionally upregulated their expression. Knockdown of FGF2 and ACLY inhibited ONECUT2-mediated HCC metastasis, whereas upregulation of FGF2 and ACLY rescued ONECUT2 knockdown-induced suppression of HCC metastasis. ONECUT2 expression was positively correlated with FGF2 and ACLY expression in human HCC tissues. HCC patients with positive coexpression of ONECUT2/FGF2 or ONECUT2/ACLY exhibited the worst prognosis. In addition, FGF2 upregulated ONECUT2 expression through the FGFR1/ERK/ELK1 pathway, which formed an FGF2-FGFR1-ONECUT2 positive feedback loop. Knockdown of ONECUT2 inhibited FGF2-induced HCC metastasis. Furthermore, the combination of FGFR1 inhibitor PD173074 with ACLY inhibitor ETC-1002 markedly suppressed ONECUT2-mediated HCC metastasis. In summary, ONECUT2 was a potential prognostic biomarker in HCC and targeting this oncogenic signaling pathway may provide an efficient therapeutic strategy against HCC metastasis.
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http://dx.doi.org/10.1038/s41419-021-04410-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8627506PMC
November 2021

Environmentally-driven metabolite and lipid variations correspond to altered bioactivities of black wolfberry fruit.

Food Chem 2022 Mar 6;372:131342. Epub 2021 Oct 6.

Guangdong Key Laboratory for Crop Germplasm Resources Preservation and Utilization, Agro-biological Gene Research Center, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China; School of Public Health, Lanzhou University, South Tianshui Road, Lanzhou 730000, China. Electronic address:

Black wolfberry is a commonly cultivated woody plant in China, and is rich in nutrients that are beneficial for human. To characterize the endogenous metabolite differences among black wolfberry fruits grown in different geographical regions, mass spectrometry-based metabolomic and lipidomic analyses were performed in black wolfberry grown in nine locations throughout five provinces in China, from which 204 primary and specialized metabolites, and 267 lipids were identified in their fruits. Three samples from Alxa Left Banner, Jinta, and Minqin showed dramatically altered metabolite profiles, displaying higher levels of phenolic acids, soluble sugars and flavonoids, but lower levels of tricarboxylic acid cycle intermediates and aromatic amino acids. Moreover, the lipid profile of the Alxa Left Banner sample was strikingly distinct from all other samples, with high levels of monogalactosyl diacylglycerol and sulfoquinovosyl diacylglycerol, which are positively correlated with their anti-inflammatory capacities. These findings thus prompt for further studies on black wolfberry fruit for their health benefits.
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http://dx.doi.org/10.1016/j.foodchem.2021.131342DOI Listing
March 2022

Genome-scale CRISPR-Cas9 knockout screening in hepatocellular carcinoma with lenvatinib resistance.

Cell Death Discov 2021 Nov 18;7(1):359. Epub 2021 Nov 18.

Department of Clinical Laboratory, Affiliated Liutie Central Hospital of Guangxi Medical University, Guangxi, China.

Lenvatinib is the first target drug approved for advanced hepatocellular carcinoma (HCC). However, the development of drug resistance is common, and the mechanisms of lenvatinib resistance and resistant targets in HCC are poorly understood. By using CRISPR/Cas9 library screening, we screened out two key resistance genes, neurofibromin 1(NF1), and dual specificity phosphatase 9 (DUSP9), as critical drivers for lenvatinib resistance in HCC. With RNAi knockdown and CRISPR/Cas9 knockout models, we further clarified the mechanisms by which NF1 loss reactivates the PI3K/AKT and MAPK/ERK signaling pathways, while DUSP9 loss activates the MAPK/ERK signaling pathways, thereby inactivating FOXO3, followed by degradation of FOXO3, finally induced lenvatinib resistance. We also screened out trametinib, a small molecule pathway inhibitor for MEK, that can be used to reverse resistance induced by NF1 and DUSP9 loss in HCC cells. Trametinib was still able to halt HCC growth even when NF1 was knocked out in mice. Collectively, the findings indicate that NF1 and DUSP9 takes critical role in lenvatinib resistance and may be novel specific targets and predictive markers for lenvatinib resistance in HCC.
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http://dx.doi.org/10.1038/s41420-021-00747-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602346PMC
November 2021

Interleukin-6 is a Strong Predictor of the Frequency of COPD Exacerbation Within 1 Year.

Int J Chron Obstruct Pulmon Dis 2021;16:2945-2951. Epub 2021 Oct 28.

The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, People's Republic of China.

Purpose: Persistent chronic inflammation of chronic obstructive pulmonary disease (COPD) is associated with poor outcomes and frequently results in acute exacerbation. Predicting the number of exacerbations is important. Because interleukin 6 (IL-6) plays an important role in inducing and maintaining chronic inflammation, we sought to observe whether IL-6 measurement can predict the frequency of acute exacerbation of COPD.

Methods: We reviewed serum IL-6 concentrations of stable COPD patients from January 2016 to December 2017 and statistically analyzed them to determine the optimal threshold value to predict the frequency of COPD acute exacerbations. Outpatients with stable COPD were then recruited between January 2018 and December 2019 and grouped into a low IL-6 group and a high IL-6 group according to this threshold value. We then compared the number of exacerbations of COPD in 1 year between the two groups.

Results: We reviewed data from 95 COPD patients, who had a median of 1.00 exacerbations in preceding year; 35 of these patients had no fewer than two. The median IL-6 concentration was 8.80 pg/mL. IL-6 and hs-CRP were positively correlated with frequency of acute exacerbation in the preceding year, COPD assessment test (CAT) score and British medical research council (mMRC) score, and negatively correlated with forced expiratory volume in one second as percentage of predicted value (FEV%pred) and FEV/FVC% (forced vital capacity). IL-6 was the risk factor of COPD patients with two or more exacerbations in 1 year. Finally, we enrolled 65 COPD patients and divided into low IL-6 group and high IL-6 group; the high IL-6 group experienced more frequent exacerbations than did the low IL-6 group.

Conclusion: An IL-6 measurement of 14.030 pg/mL or more is a risk factor for ≥2 acute exacerbations of COPD in the following year.
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http://dx.doi.org/10.2147/COPD.S332505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560075PMC
November 2021

Homeobox Genes in Cancers: From Carcinogenesis to Recent Therapeutic Intervention.

Front Oncol 2021 14;11:770428. Epub 2021 Oct 14.

Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The homeobox (HOX) genes encoding an evolutionarily highly conserved family of homeodomain-containing transcriptional factors are essential for embryogenesis and tumorigenesis. HOX genes are involved in cell identity determination during early embryonic development and postnatal processes. The deregulation of HOX genes is closely associated with numerous human malignancies, highlighting the indispensable involvement in mortal cancer development. Since most HOX genes behave as oncogenes or tumor suppressors in human cancer, a better comprehension of their upstream regulators and downstream targets contributes to elucidating the function of HOX genes in cancer development. In addition, targeting HOX genes may imply therapeutic potential. Recently, novel therapies such as monoclonal antibodies targeting tyrosine receptor kinases, small molecular chemical inhibitors, and small interfering RNA strategies, are difficult to implement for targeting transcriptional factors on account of the dual function and pleiotropic nature of HOX genes-related molecular networks. This paper summarizes the current state of knowledge on the roles of HOX genes in human cancer and emphasizes the emerging importance of HOX genes as potential therapeutic targets to overcome the limitations of present cancer therapy.
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http://dx.doi.org/10.3389/fonc.2021.770428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551923PMC
October 2021

Therapeutic Values of Myeloid-Derived Suppressor Cells in Hepatocellular Carcinoma: Facts and Hopes.

Cancers (Basel) 2021 Oct 13;13(20). Epub 2021 Oct 13.

Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

One of the major challenges in hepatocellular carcinoma (HCC) treatment is drug resistance and low responsiveness to systemic therapies, partly due to insufficient T cell infiltration. Myeloid-derived suppressor cells (MDSCs) are immature marrow-derived cell populations with heterogeneity and immunosuppression characteristics and are essential components of the suppressive tumor immune microenvironment (TIME). Increasing evidence has demonstrated that MDSCs are indispensable contributing factors to HCC development in a T cell-dependent or non-dependent manner. Clinically, the frequency of MDSCs is firmly linked to HCC clinical outcomes and the effectiveness of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs). Furthermore, MDSCs can also be used as prognostic and predictive biomarkers for patients with HCC. Therefore, treatments reprograming MDSCs may offer potential therapeutic opportunities in HCC. Here, we recapitulated the dynamic relevance of MDSCs in the initiation and development of HCC and paid special attention to the effect of MDSCs on T cells infiltration in HCC. Finally, we pointed out the potential therapeutic effect of targeting MDSCs alone or in combination, hoping to provide new insights into HCC treatment.
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http://dx.doi.org/10.3390/cancers13205127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534227PMC
October 2021

mA Methylation Modification Patterns and Tumor Microenvironment Infiltration Characterization in Pancreatic Cancer.

Front Immunol 2021 20;12:739768. Epub 2021 Sep 20.

Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Recent studies have shown that RNA N-methyladenosine (mA) modification plays an important part in tumorigenesis and immune-related biological processes. However, the comprehensive landscape of immune cell infiltration characteristics in the tumor microenvironment (TME) mediated by mA methylation modification in pancreatic cancer has not yet been elucidated. Based on consensus clustering algorithm, we identified two mA modification subtypes and then determined two mA-related gene subtypes among 434 pancreatic cancer samples. The TME characteristics of the identified gene subtypes were highly consistent with the immune-hot phenotype and the immune-cold phenotype respectively. According to the mA score extracted from the mA-related signature genes, patients can be divided into high and low mA score groups. The low score group displayed a better prognosis and relatively strong immune infiltration. Further analysis showed that low mA score correlated with lower tumor mutation burden and PD-L1 expression, and indicated a better response to immunotherapy. In general, mA methylation modification is closely related to the diversity and complexity of immune infiltration in TME. Evaluating the mA modification pattern and immune infiltration characteristics of individual tumors can help deepen our understanding of the tumor microenvironment landscape and promote a more effective clinical practice of immunotherapy.
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http://dx.doi.org/10.3389/fimmu.2021.739768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488339PMC
December 2021

Application of laser speckle blood perfusion imaging in the evaluation of erectile function in rats.

Andrologia 2022 Feb 4;54(1):e14264. Epub 2021 Oct 4.

Department of Urology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Intracavernosal pressure measurement is the gold standard for evaluating erectile function in experimental animals, but it has the shortcoming of being invasive. This study aimed to explore the application of laser speckle perfusion imaging in evaluating erectile function in rats. Sixty Sprague Dawley rats were randomly divided into the sham operation and model groups (n = 30 each). A rat model of neuroinjury erectile dysfunction was established by surgically damaging the bilateral cavernous nerves in the model group. Simulated surgery was performed in the sham operation group; the nerves were not damaged. Erectile function was evaluated by comparing the changes in intracavernosal pressure and blood flow fluctuations when the cavernous nerve was stimulated using the same voltage parameters. Intracavernosal pressure in the model group was significantly lower than that in the other group when using 2.5 V. No significant difference was found in cavernous blood flow fluctuation between the two groups when using 0.5 V. Cavernous blood flow fluctuation in the model group after 2.5 V, 5 V and 7.5 V stimulations was significantly lower than that in the sham operation group. Evaluating erectile function in rats is feasible by measuring the cavernous blood flow using laser speckle perfusion imaging.
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http://dx.doi.org/10.1111/and.14264DOI Listing
February 2022

The ceRNA PVT1 inhibits proliferation of ccRCC cells by sponging miR-328-3p to elevate FAM193B expression.

Aging (Albany NY) 2021 09 13;13(17):21712-21728. Epub 2021 Sep 13.

Tongji University School of Medicine, Shanghai 20092, Shanghai, China.

Clear cell renal cell carcinoma (ccRCC) is a common and fatal malignancy. Long noncoding RNAs (lncRNAs) have emerged as crucial biomarkers and regulators in many cancers, warranting the detailed investigation of their biological functions and molecular mechanisms. In this study, we explored the role and mechanism of plasmacytoma variant translocation 1 (PVT1), a competitive endogenous RNA (ceRNA) in ccRCC tissues and . We found that PVT1 is upregulated in ccRCC cells and promoted cell proliferation. Bioinformatic analysis, dual-luciferase reporter assays, argonaute 2-RNA immunoprecipitation (AGO2-RIP), quantitative PCR arrays, western blot assay, and rescue experiments were conducted to explore the underlying mechanisms of PVT1. Our analyses revealed that miR-328-3p was a direct target of PVT1 and that FAM193B was a direct target of miR-328-3p. FAM193B is upregulated in ccRCC tissues and promotes cell proliferation by activating the MAPK/ERK and PI3K/AKT pathways. Our results indicated that PVT1 promotes ccRCC cells proliferation by sponging miR-328-3p to upregulate FAM193B and activate the MAPK/ERK and PI3K/AKT pathways. Collectively, these results suggest that PVT1- miR-328-3p-FAM193B loop could serve as a potential biomarker and therapeutic target for ccRCC.
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http://dx.doi.org/10.18632/aging.203514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457591PMC
September 2021

The incidence of influenza in children was decreased in the first flu season after COVID-19 pandemic in Wuhan.

J Infect Public Health 2021 Sep 27;14(9):1279-1281. Epub 2021 Aug 27.

Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China. Electronic address:

Wuhan, China was the first city to discover COVID-19. With the government's macro-control and the active cooperation of the public, the spread of COVID-19 has been effectively controlled. In order to understand the additional impact of these measures on the prevalence of common influenza, we have collected flu test data from the Pediatric Clinic of Zhongnan Hospital of Wuhan University from September to December 2020, and compared them with the same period in 2018 and 2019. It is found that compared with the same period in 2018 and 2019, the rate of children's influenza activity in 2020 has significantly decreased, which indicates that the protective measures against COVID-19 have effectively reduced the level of influenza activity.
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http://dx.doi.org/10.1016/j.jiph.2021.08.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393498PMC
September 2021

Whole-transcriptome analysis of rat cavernosum and identification of circRNA-miRNA-mRNA networks to investigate nerve injury erectile dysfunction pathogenesis.

Bioengineered 2021 12;12(1):6516-6528

Department of Urology and Andrology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.

There is growing evidence that circular RNAs (circRNAs) play a vital role in many kinds of diseases, including erectile dysfunction (ED). Nevertheless, the role of circRNAs in cavernous nerve-damaging ED (CNI-ED) is unknown. Here, we aimed to discover novel circRNAs, probed their potential role in the CNI-ED, and construct a ceRNA network of circRNAs. Twelve male Sprague Dawley rats were randomly divided into 2 groups by us: bilateral cavernous nerve crush (BCNC) and control groups. Four weeks after surgery, the spongy smooth muscle tissue of the rat penis was sequenced using high-throughput full transcriptome sequencing. We analyzed the expression of circRNAs, miRNAs, and mRNAs in the two groups. Twenty circRNAs with significantly different expressions were selected for RT-qPCR. CeRNA network of circRNAs was established using Cytoscape. GO and KEGG analysis was done by R package. Sequencing showed that 4,587 circRNAs, 762 miRNAs, and 21,661 mRNAs were dysregulated in the BCNC group. The top 20 differentially expressed circRNAs were further verified via RT-qPCR. The ceRNA network contained ten circRNAs, six miRNAs, and 227 mRNAs, including 23 circRNA-miRNA pairs and 227 miRNA-mRNA pairs. GO and KEGG analysis suggested that these ten circRNAs could main regulate energy metabolism processes. A protein-protein interaction network was constructed with the mRNAs in ceRNA network, and five hub genes were identified. Our study revealed a potential link between circRNAs, miRNAs, and mRNAs in CNI-ED, suggesting that circRNAs may contribute to the occurrence of ED by regulating the cellular energy metabolism in CNI-ED.
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http://dx.doi.org/10.1080/21655979.2021.1973863DOI Listing
December 2021

A Novel Signature Constructed by Immune-Related LncRNA Predicts the Immune Landscape of Colorectal Cancer.

Front Genet 2021 9;12:695130. Epub 2021 Aug 9.

Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Colorectal cancer (CRC) has the characteristics of high morbidity and mortality. LncRNA not only participates in the progression of CRC through genes and transcription levels, but also regulates the tumor microenvironment and leads to the malignant phenotype of tumors. Therefore, we identified immune-related LncRNAs for the construction of clinical prognostic model. We searched The Cancer Genome Atlas (TCGA) database for original data. Then we identified differentially expressed irlncRNA (DEirlncRNA), which was paired and verified subsequently. Next, univariate analysis, Lasso and Cox regression analysis were performed on the DEirlncRNA pair. The ROC curve of the signature was drawn, and the optimal cut-off value was found. Then the cohort was divided into a high-risk and a low-risk group. Finally, we re-evaluated the signature from different perspectives. A total of 16 pairs of DEirlncRNA were included in the construction of the model. After regrouping according to the cut-off value of 1.275, the high-risk group showed adverse survival outcomes, progressive clinicopathological features, specific immune cell infiltration status, and high sensitivity to some chemotherapy drugs. In conclusion, we constructed a signature composed of immune-related LncRNA pair with no requirement of the specific expression level of genes, which shows promising clinical predictive value in CRC patients.
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http://dx.doi.org/10.3389/fgene.2021.695130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381735PMC
August 2021

Efficacy of circulating microRNA-130b and blood routine parameters in the early diagnosis of gastric cancer.

Oncol Lett 2021 Oct 10;22(4):725. Epub 2021 Aug 10.

Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi University of Science and Technology, Liuzhou, Guangxi Zhuang Autonomous Region 545005, P.R. China.

Patients with gastric cancer (GC) have a poor prognosis, which is mainly due to the low rate of early diagnosis. The present study aimed to evaluate whether circulating microRNA-130b (miR-130b) and blood routine parameters [neutrophil count (N#), lymphocyte count (L#), monocyte count (M#), neutrophil percentage (N%), lymphocyte percentage (L%), monocyte percentage (M%), hemoglobin (Hb) level, hematocrit (Hct), red blood cell distribution width (RDW), platelet count, platelet distribution width (PDW), mean platelet volume (MPV), MPV to platelet count ratio (MPV/PC), monocyte to lymphocyte ratio (MLR), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR)] are useful biomarkers for GC, early stage GC (EGC) and precancerous lesion (Pre) detection, and to identify more effective diagnostic models by combining circulating blood markers. Circulating levels of M#, M%, RDW-coefficient of variation (RDW-CV), MPV, PDW, MLR and NLR were significantly higher, and the levels of Hb and L% were significantly lower in patients with GC and Pre compared with those in healthy controls (NCs) (all P<0.05). The N#, N% and PLR in patients with GC were significantly higher and the Hct was significantly lower than those in the NCs (all P<0.05). The values of MPV/PC were significantly higher in the Pre cohort compared with those in the NCs. The area under the curve (AUC) of the receiver operating characteristic curve of potential biomarkers for GC was 0.634-0.887 individually, and this increased to 0.978 in the combination model of miR-130b-PDW-MLR-Hb. Additionally, the values for RDW-CV, PLR, NLR, N# and N% were positively correlated with cancer stage, while the values for MPV, L#, L%, Hb and Hct were negatively correlated with cancer stage. Furthermore, the circulating levels of miRNA-130b, and the values for NLR, RDW-CV, PDW, M%, red blood cell count, Hct, Hb and MLR differed between the EGC and NC groups. The AUC values of these biomarkers were 0.6491-0.911 individually in the diagnosis of EGC, and these increased to 0.960 in combination. In addition, the AUC values for miR-130b, RDW-CV, MPV/PC ratio, MLR, NLR, PDW, L%, M%, M# and Hb in the diagnosis of Pre were 0.638-0.811 individually. The dual-model of miR-130b-PDW manifested the largest AUC of 0.896 in the diagnosis of Pre, and the sensitivity and accuracy were increased when miR-130b and PDW were combined. All these results suggested that circulating miR-130b and blood routine parameters might be potential biomarkers, and combinations of measurements of these biomarkers may improve the GC, EGC and Pre diagnostic accuracy.
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http://dx.doi.org/10.3892/ol.2021.12986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371962PMC
October 2021

TDO2 Was Downregulated in Hepatocellular Carcinoma and Inhibited Cell Proliferation by Upregulating the Expression of p21 and p27.

Biomed Res Int 2021 13;2021:4708439. Epub 2021 Aug 13.

Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Tryptophan-2,3-dioxygenase (TDO2) converts tryptophan into kynurenine in the initial limiting step of the kynurenine pathway. During the past decade, the overexpression of TDO2 has been found in various human tumors. However, the role of TDO2 in hepatocellular carcinoma is controversial, and we sought to clarify it in this study.

Methods: Western blot analysis and immunochemistry were used to detect the expression of TDO2 in human tissue specimens. The effect of TDO2 on cell proliferation in vitro was assessed using CCK8 and colony formation assays, and a xenograft mouse model was used to detect the effect of TDO2 on tumor growth in vivo. Flow cytometry was used to assess the cell cycle status.

Results: Low TDO2 expression was found in HCC and was associated with poor prognosis and adverse clinical outcomes. Conversely, TDO2 could restrain the proliferation of HCC cells in vivo and in vitro. Furthermore, TDO2 upregulated the expression of p21 and p27, inducing cell-cycle arrest.

Conclusions: The loss of TDO2 expression in HCC was correlated with a poor prognosis and adverse clinical outcomes. At the same time, TDO2 could restrain the growth of HCC in vivo and in vitro. The results indicate that TDO2 is a potential biomarker and therapeutic target for HCC.
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http://dx.doi.org/10.1155/2021/4708439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378971PMC
September 2021

Molecular determinants for regulation of G3BP1/2 phase separation by the SARS-CoV-2 nucleocapsid protein.

Cell Discov 2021 Aug 17;7(1):69. Epub 2021 Aug 17.

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Paediatrics, West China Second University Hospital, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu, China.

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http://dx.doi.org/10.1038/s41421-021-00306-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8368218PMC
August 2021

MRI of nasopharyngeal carcinoma: parapharyngeal subspace involvement has prognostic value and influences T-staging in the IMRT era.

Eur Radiol 2022 Jan 29;32(1):262-271. Epub 2021 Jul 29.

Department of Radiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, People's Republic of China.

Objectives: To identify the prognosis of parapharyngeal space involvement (PPSI) based on the number of subspaces involved (pre-styloid space, carotid space (CS), areas outside the CS) and explore its significance for current T-staging in patients with nasopharyngeal carcinoma (NPC).

Methods: PPSI was retrospectively identified in 1224 patients with non-disseminated NPC at two centers on MRI and separated into four invasion patterns: pattern A (only post-styloid space), pattern B (post-styloid space, CS extension), pattern C (post-styloid space, pre-styloid space extension), and pattern D (all spaces). The Kaplan-Meier analysis and multivariate Cox regression models were used.

Results: PPSI was diagnosed in 63.4% of cases, with patterns A, B, C, and D in 14.3%, 3.8%, 25.3%, and 18.6% of cases, respectively. No prognostic heterogeneity was observed between pattern B and pattern C (p > 0.05). Thus, the degree of PPSI was based on the number of subspaces involved: grade 0 (none), grade 1 (one), grade 2 (two), and grade 3 (three), which could independently predict overall survival (OS) (p < 0.001). T3 patients with grade 0/1 PPSI (slight-T3) had a better prognosis than those with grade 2/3 PPSI (severe-T3) in terms of OS, locoregional-free survival (LRFS), and progression-free survival (PFS) (all p < 0.001), whose hazard ratios were higher and lower than those with T1 and T2, respectively. Combining the T2 and slight-T3 groups as the proposed T2 provided significant differences in OS, LRFS, and PFS between T2 and T3 (all p < 0.05).

Conclusions: The risk of death increased with the number of parapharyngeal subspaces involved. The degree of PPSI is recommended to optimize T3 heterogeneity.

Key Points: • Parapharyngeal space involvement was proposed to differentiate patient risk groups based on the number of involved subspaces: grade 0 (none), grade 1 (one), grade 2 (two), or grade 3 (three). • The degree of parapharyngeal space involvement was an independent negative prognosticator for OS. • The degree of parapharyngeal space involvement may influence T-staging in patients with nasopharyngeal carcinoma.
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http://dx.doi.org/10.1007/s00330-021-08113-3DOI Listing
January 2022

IL-1β-Induced Elevation of Solute Carrier Family 7 Member 11 Promotes Hepatocellular Carcinoma Metastasis Through Up-regulating Programmed Death Ligand 1 and Colony-Stimulating Factor 1.

Hepatology 2021 12 27;74(6):3174-3193. Epub 2021 Aug 27.

Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background And Aims: Because of a paucity of effective treatment options, metastasis is still a major cause for HCC-associated mortality. The molecular mechanism of inflammation-induced HCC metastasis is open for study. Here, we characterized the function of solute carrier family 7 member 11 (SLC7A11) in inflammation-related HCC metastasis and probed therapy strategies for this subpopulation of patients.

Approach And Results: Elevated expression of SLC7A11 was positively correlated with poor tumor differentiation, and higher tumor-nodule-metastasis stage, and indicated poor prognosis in human HCC. SLC7A11 increased HIF1α expression through reducing α-ketoglutarate (αKG) level by exporting glutamate. SLC7A11 up-regulated programmed death ligand 1 (PD-L1) and colony-stimulating factor 1 (CSF1) expression through αKG-HIF1α cascade. SLC7A11 overexpression in HCC cells promoted intratumoral tumor-associated macrophage (TAM) and myeloid-derived suppressor cell (MDSC) infiltration through the CSF1/colony-stimulating factor 1 receptor (CSF1R) axis, whereas knockdown of CSF1 attenuated SLC7A11-mediated intratumoral TAM and MDSC infiltration and HCC metastasis. Depletion of either TAMs or MDSCs decreased SLC7A11-mediated HCC metastasis. Furthermore, the combination of CSF1R inhibitor BZL945 and anti-PD-L1 antibody blocked SLC7A11-induced HCC metastasis. In addition, IL-1β up-regulated SLC7A11 expression through the interleukin-1 receptor type 1 (IL-1R1)/extracellular signal-regulated kinase/specificity protein 1 pathway. SLC7A11 knockdown impaired IL-1β-promoted HCC metastasis. Anakinra, an IL-1R1 antagonist, reversed IL-1β-promoted HCC metastasis. In human HCC tissues, SLC7A11 expression was positively associated with HIF1α, PD-L1, and CSF1 expression and intratumoral TAM and MDSC infiltration.

Conclusions: IL-1β-induced SLC7A11 overexpression up-regulated PD-L1 and CSF1 through the αKG/HIF1α axis, which promoted TAM and MDSC infiltration. Interruption of this oncogenic loop may provide a promising therapy strategy for the inhibition of SLC7A11-mediated HCC metastasis.
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http://dx.doi.org/10.1002/hep.32062DOI Listing
December 2021

Metabolomics Analysis of Litchi Leaves during Floral Induction Reveals Metabolic Improvement by Stem Girdling.

Molecules 2021 Jul 2;26(13). Epub 2021 Jul 2.

Agro-Biological Gene Research Center, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China.

Prolonged exposure to cold temperatures often results in a relatively low flowering rate in litchi ( Sonn.) trees with younger leaves. This study aimed to verify the impact of stem girdling on litchi flowering by identifying and characterizing the induced metabolic changes. After a 60 day exposure to cold treatment at 15 °C/10 °C (12 h/12 h), the flowering rate of the girdled trees was 100%, while that of the non-girdled trees was 20%, indicating that girdling improved litchi flowering at its turning stage. The metabolic profiles of litchi leaves with and without stem girdling during floral induction were compared and 505 metabolites potentially associated with litchi flowering were detected. Most metabolites were involved in the metabolism of starch and sucrose, fatty acid, and phenylpyruvic acid. The metabolic pathways concerned with the biosynthesis of epinephrine, sucrose, and d-maltose were induced in leaves after girdling treatment. The level of galactitol, phenylpyruvic acid, acetyl-CoA, linoleic acid, alpha-linolenic acid, and 13-HPOT biosynthesis remained stable in the leaves from girdled trees but changed drastically in the leaves from non-girdled trees. In addition, 379 metabolites concerning flowering rate were characterized. Metabolism pathways of starch and sucrose, galactose, and linoleic acid are of great significance to the flowering of litchi. Linoleic acid exhibited the most significant variations between girdled trees and non-girdled trees with fold changes of up to 13.62. These results contribute to understanding the biological mechanism of litchi floral induction and the metabolic changes after stem girdling.
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http://dx.doi.org/10.3390/molecules26134048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271987PMC
July 2021

Comprehensive analysis of an immune-related ceRNA network in identifying a novel lncRNA signature as a prognostic biomarker for hepatocellular carcinoma.

Aging (Albany NY) 2021 07 8;13(13):17607-17628. Epub 2021 Jul 8.

Department of Hepatobiliary Surgery I, General Surgery Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

The function of competitive endogenous RNA (ceRNA) network in the immune regulation of hepatocellular carcinoma (HCC) is unclear. Our study aimed to construct an immune-related ceRNA network and develop an immune-related long noncoding RNA (lncRNA) signature to assess the prognosis of HCC patients and to optimize the treatment methods. We firstly constructed a ceRNA regulatory network for HCC using differentially expressed lncRNAs, mRNAs and microRNAs (miRNAs) from the Cancer Genome Atlas. A signature was constructed by 11 immune-related prognostic lncRNAs from the ceRNA network. The survival analysis and receiver operating characteristic analysis validated the reliability of the signature. Multivariate Cox regression analysis revealed that the signature could act an independent prognostic indicator. This signature also showed high association with immune cell infiltration and immune check blockades. LINC00491 was identified as the hub lncRNA in the signature. and evidence demonstrated that silencing of LINC00491 significantly inhibited HCC growth. Finally, 59 lncRNAs, 21 miRNAs, and 26 mRNAs were obtained to build the immune-related ceRNA network for HCC. In conclusion, our novel immune-related lncRNA prognostic signature and the immune-related ceRNA network might provide in-depth insights into tumor-immune interaction of HCC and promote better individual treatment strategies in HCC patients.
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http://dx.doi.org/10.18632/aging.203250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312417PMC
July 2021

Intra-arterial infusion chemotherapy utilizing cisplatin inhibits bladder cancer by decreasing the fibrocytic myeloid-derived suppressor cells in an m6A-dependent manner.

Mol Immunol 2021 09 26;137:28-40. Epub 2021 Jun 26.

Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Intra-arterial infusion chemotherapy (IAIC), using immunomodulatory cisplatin, is a novel treatment for bladder cancer (BC) that allows the delivery of specific drugs to the local malignant lesion. To explore the immunomodulatory effect of cisplatin during IAIC, we detected the proportion of immunosuppressed cells in BC tissue from eight BC patients, with the reduction of myeloid-derived suppressor cells (MDSCs), more specifically fibrocytic-MDSCs (f-MDSCs). Further, we demonstrated that cisplatin inhibits their proliferation and immunosuppressive activity. f-MDSCs promote tumor proliferation and metastasis in the BC immune environment. Then, we analyzed the genetic differences detected in samples before and after chemotherapy and found that granulocyte colony-stimulating factors (G-CSF) decreased after IAIC. Furthermore, G-CSF methylation decreased following treatment with cisplatin. Specifically, treatment with cisplatin decreased the methylase (METTL3) levels in BC cells, which is important for G-CSF production. Collectively, cisplatin decreased the number of f-MDSCs during IAIC, by blocking G-CSF methylation via targeting METTL3.
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http://dx.doi.org/10.1016/j.molimm.2021.06.012DOI Listing
September 2021

The Emerging Roles of circFOXO3 in Cancer.

Front Cell Dev Biol 2021 4;9:659417. Epub 2021 Jun 4.

Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs which are mainly formed by reverse splicing of precursor mRNAs. They are relatively stable and resistant to RNase R because of their covalently closed structure without 5' caps or 3' poly-adenylated tails. CircRNAs are widely expressed in eukaryotic cells and show tissue, timing, and disease specificity. Recent studies have found that circRNAs play an important role in many diseases. In particular, they affect the proliferation, invasion and prognosis of cancer by regulating gene expression. CircRNA Forkhead box O3 (circFOXO3) is a circRNA confirmed to be abnormally expressed in a variety of cancers, including prostate cancer, hepatocellular carcinoma, glioblastoma, bladder cancer, and breast cancer, etc. At present, the feature of circFOXO3 as a molecular sponge is widely studied to promote or inhibit the development of cancers. However, the diverse functions of circFOXO3 have not been fully understood. Hence, it is important to review the roles of circFOXO3 in cancers. This review has summarized and discussed the roles and molecular mechanism of circFOXO3 and its target genes in these cancers, which can help to enrich our understanding to the functions of circRNAs and carry out subsequent researches on circFOXO3.
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http://dx.doi.org/10.3389/fcell.2021.659417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213346PMC
June 2021

ST-segment elevation myocardial infarction in post-COVID-19 patients: A case series.

Ann Acad Med Singap 2021 05;50(5):425-430

Department of Cardiology, Tan Tock Seng Hospital, Singapore.

Coronavirus disease 2019 (COVID-19) is associated with an increased risk of thromboembolic events in the acute setting. However, the abnormal thrombotic diathesis is not known to persist into the recovery phase of COVID-19 infection. We described 3 cases of ST-segment elevation myocardial infarction in healthy male patients who recovered from COVID-19 with no prior cardiovascular risk factors. They shared features of elevated von Willebrand factor antigen, factor VIII and D-dimer level. One patient had a borderline positive lupus anticoagulant. Intravascular ultrasound of culprit vessels revealed predominantly fibrotic plaque with minimal necrotic core. Clot waveform analysis showed parameters of hypercoagulability. They were treated with dual antiplatelet therapy, angiotensin-converting-enzyme inhibitor, beta blocker and statin. These cases highlight the strong thrombogenic nature of COVID-19 that persisted among patients who recovered from infection. Several suspected mechanisms could explain the association between vascular thrombosis in the convalescent period (endothelial dysfunction, hypercoagulability, systemic inflammatory response and vasculopathy). Additional studies on "long COVID" are essential for identifying endotheliopathy and thrombotic sequalae.
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May 2021

IGF1-mediated HOXA13 overexpression promotes colorectal cancer metastasis through upregulating ACLY and IGF1R.

Cell Death Dis 2021 06 1;12(6):564. Epub 2021 Jun 1.

Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei, China.

Metastasis is the major reason for the high mortality of colorectal cancer (CRC) patients and its molecular mechanism remains unclear. Here, we report a novel role of Homeobox A13 (HOXA13), a member of the Homeobox (HOX) family, in promoting CRC metastasis. The elevated expression of HOXA13 was positively correlated with distant metastasis, higher AJCC stage, and poor prognosis in two independent CRC cohorts. Overexpression of HOXA13 promoted CRC metastasis whereas downregulation of HOXA13 suppressed CRC metastasis. Mechanistically, HOXA13 facilitated CRC metastasis by transactivating ATP-citrate lyase (ACLY) and insulin-like growth factor 1 receptor (IGF1R). Knockdown of ACLY and IGFIR inhibited HOXA13-medicated CRC metastasis, whereas ectopic overexpression of ACLY and IGFIR rescued the decreased CRC metastasis induced by HOXA13 knockdown. Furthermore, Insulin-like growth factor 1 (IGF1), the ligand of IGF1R, upregulated HOXA13 expression through the PI3K/AKT/HIF1α pathway. Knockdown of HOXA13 decreased IGF1-mediated CRC metastasis. In addition, the combined treatment of ACLY inhibitor ETC-1002 and IGF1R inhibitor Linsitinib dramatically suppressed HOXA13-mediated CRC metastasis. In conclusion, HOXA13 is a prognostic biomarker in CRC patients. Targeting the IGF1-HOXA13-IGF1R positive feedback loop may provide a potential therapeutic strategy for the treatment of HOXA13-driven CRC metastasis.
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http://dx.doi.org/10.1038/s41419-021-03833-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169856PMC
June 2021

Accumulation of CD45RO+CD8+ T cells is a diagnostic and prognostic biomarker for clear cell renal cell carcinoma.

Aging (Albany NY) 2021 05 19;13(10):14304-14321. Epub 2021 May 19.

Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.

Renal cell carcinoma is characterized by high immunogenicity and infiltration of immune cells. CD45RO+CD8+ T cells are well known as a critical role in host defense of the immune environment. However, their role in clear cell renal carcinoma (ccRCC) remains unknown. To elucidate the clinical importance of CD45RO+CD8+ T cells in ccRCC as well as its underlying mechanism, we analyzed several types of peripheral immune cells from 274 patients with ccRCC who have received radical or partial nephrectomy and 350 healthy people. Flow cytomety assays showed there was no significant difference in the proportions of CD8+ T cells and its subtypes other than CD45RO+/CD45RA+CD8+ cells. Both gene and protein expression levels of CD45RO in ccRCC tissues were decreased. CD45RO+CD8+ T cells showed increased proliferative abilities but decreased apoptotic abilities through MAPK signaling activation in ccRCC. High expression level of CD45RO+CD8+ T cells inhibited ccRCC progression, including proliferation, invasion, as well as autophagy of ccRCC through many signaling pathways. Bioinformatics and immunohistochemical chip analysis measured gene and protein levels of CD45RO and other related proteins. The combination of UCHL1, HMGB3, and CD36 has diagnostic value in ccRCC and is able to predict prognosis. Collectively, CD45RO+CD8+ T cells play a critical role in ccRCC progression and may be regarded as clinical indicators.
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http://dx.doi.org/10.18632/aging.203045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202838PMC
May 2021
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