ORCID Profile
0000-0002-1028-6319
Current Organisations
The University of Tennessee Knoxville
,
Clinical Medical Research Center, The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, Shenzhen, 518020, China.
,
Southern Medical University, Affiliated Shenzhen Longhua Hospital
,
People's Hospital of Longhua, The Affiliated Hospital of Southern Medical University, Shenzhen
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Publisher: Bentham Science Publishers Ltd.
Date: 14-10-2019
DOI: 10.2174/1389202920666190820122126
Abstract: Long non-coding RNAs (lncRNAs) are emerging as important regulators in the modulation of virus infection by targeting mRNA transcription. However, their roles in chronic hepatitis B (CHB) remain to be elucidated. The study aimed to explore the lncRNAs and mRNA expression profiles in CHB and asymptomatic HBsAg carriers (ASC) and construct mRNA-lncRNA co-expression profile and ceRNA networks to identify the potential targets of diagnosis and treatment in CHB. We determined the expression profiles of lncRNAs and mRNAs in CHB and ASC using microarray analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore their function. We also constructed coexpression, cis-regulatory, and competing endogenous RNA (ceRNA) networks with bioinformatics methods. We identified 1634 mRNAs and 5550 lncRNAs that were differentially expressed between CHB and ASC. Significantly enriched GO terms and pathways were identified, many of which were linked to immune processes and inflammatory responses. Co-expression analysis showed 1196 relationships between the top 20 up/downregulated lncRNAs and mRNA, especially 213 lncRNAs interacted with ZFP57. The ZFP57-specific ceRNA network covered 3 lncRNAs, 5 miRNAs, and 17 edges. Cis-correlation analysis showed that lncRNA T039096 was paired with the most differentially expressed gene, ZFP57. Moreover, by expending the clinical s les size, the qRT-PCR results showed that the expression of ZFP57 and T039096 increased in CHB compared to ASC. Our study provides insights into the roles of mRNA and lncRNA networks in CHB, highlighting potential applications of lncRNA-T039096 and mRNA-ZFP57 for diagnosis and treatment.
Publisher: Springer Science and Business Media LLC
Date: 04-01-2021
DOI: 10.1186/S13046-020-01803-8
Abstract: Hepatitis B virus (HBV) infection is a crucial risk factor for hepatocellular carcinoma (HCC). However, its underlying mechanism remains understudied. Microarray analysis was conducted to compare the genes and miRNAs in liver tissue from HBV-positive and HBV-negative HCC patients. Biological functions of these biomarkers in HBV-related HCC were validated via in vitro and in vivo experiments. Furthermore, we investigated the effect of HBV on the proliferation and migration of tumor cells in HBV-positive HCC tissue. Bioinformatics analysis was then performed to validate the clinical value of the biomarkers in a large HCC cohort. We found that a gene, MINPP1 from the glycolytic bypass metabolic pathway, has an important biological function in the development of HBV-positive HCC. MINPP1 is down-regulated in HBV-positive HCC and could inhibit the proliferation and migration of the tumor cells. Meanwhile, miRNA-30b-5p was found to be a stimulator for the proliferation of tumor cell through glycolytic bypass in HBV-positive HCC. More importantly, miRNA-30b-5p could significantly downregulate MINPP1 expression. Metabolic experiments showed that the miRNA-30b-5p/MINPP1 axis is able to accelerate the conversion of glucose to lactate and 2,3-bisphosphoglycerate (2,3-BPG). In the HBV-negative HCC cells, miRNA-30b-5p/MINPP1 could not regulate the glycolytic bypass to promote the tumorigenesis. However, once HBV was introduced into these cells, miRNA-30b-5p/MINPP1 significantly enhanced the proliferation, migration of tumor cells, and promoted the glycolytic bypass. We further revealed that HBV infection promoted the expression of miRNA-30b-5p through the interaction of HBV protein P (HBp) with FOXO3. Bioinformatics analysis on a large cohort dataset showed that high expression of MINPP1 was associated with favorable survival of HBV-positive HCC patients, which could lead to a slower progress of this disease. Our study found that the HBp/FOXO3/miRNA-30b-5p/MINPP1 axis contributes to the development of HBV-positive HCC cells through the glycolytic bypass. We also presented miRNA-30b-5p/MINPP1 as a novel biomarker for HBV-positive HCC early diagnosis and a potential pharmaceutical target for antitumor therapy.
Publisher: Mary Ann Liebert Inc
Date: 10-2019
Publisher: AME Publishing Company
Date: 04-2019
Location: China
Location: United States of America
Location: No location found
Location: China
Location: China
Location: China
Location: China
Location: China
No related grants have been discovered for Wenbiao Chen.