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撤稿文章:微小RNA-1271通过靶向沉默调节蛋白1调控乙型肝炎病毒相关肝细胞癌中乙型肝炎病毒的复制、细胞增殖和凋亡

Retracted Article: MicroRNA-1271 modulates hepatitis B virus replication, cell proliferation and apoptosis in hepatitis B virus-related hepatocellular carcinoma by targeting SIRT1.

作者信息

Tang Fei, Wang Fengmei, Lv Hongmin, Xiang Huiling, Liu Yi, Liu Ping

机构信息

Department of Gastroenterology and Hepatology, The Third Central Clinical College of Tianjin Medical University (Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Artificial Cells) No. 83 Jintang Road, Hedong District Tianjin 317000 China

Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin (Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Artificial Cells) Tianjin China.

出版信息

RSC Adv. 2019 Dec 2;9(68):39904-39913. doi: 10.1039/c9ra08248d.

Abstract

Chronic hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC). Certain studies have revealed that microRNAs play crucial roles in HBV-related HCC. The aim of this study was to investigate the effects of microRNA-1271 (miR-1271) on HBV replication, cell proliferation and apoptosis in HBV-related HCC. The expression of HBV DNA and miR-1271 was detected by quantitative real time-polymerase chain reaction (qRT-PCR). The mRNA and protein levels of SIRT1 were detected by qRT-PCR and western blot analysis, respectively. HBV replication was assessed by the expression of HBV DNA and the levels of HBsAg and HBeAg. Cell proliferation was assessed by cell counting kit-8 (CCK-8) and 5-bromo-2-deoxyuidine (BrdU) assay, and apoptosis was evaluated by flow cytometry assay, enzyme-linked immunosorbent assay (ELISA) and the activity of caspase-3. The relationship between miR-1271 and SIRT1 was predicated by online software and confirmed by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) and pull-down assay. We first found that the expression of miR-1271 was downregulated and SIRT1 was upregulated in both HBV-related HCC tissues and cells. Overexpression of miR-1271 inhibited HBV replication and cell proliferation whilst promoting apoptosis in HBV-related HCC cells. Subsequently, SIRT1 was identified as a target of miR-1271. Moreover, overexpression of SIRT1 reversed the effects of miR-1271 overexpression on HBV replication, cell proliferation and apoptosis in HBV-related HCC cells. In conclusion, our study demonstrated that miR-1271 inhibited HBV replication and proliferation and promoted apoptosis of HBV-related HCC cells targeting SIRT1, which might contribute to the diagnosis and therapy of HBV-related HCC.

摘要

慢性乙型肝炎病毒(HBV)感染是肝细胞癌(HCC)的主要病因。某些研究表明,微小RNA在HBV相关的HCC中起关键作用。本研究旨在探讨微小RNA-1271(miR-1271)对HBV相关HCC中HBV复制、细胞增殖和凋亡的影响。通过定量实时聚合酶链反应(qRT-PCR)检测HBV DNA和miR-1271的表达。分别通过qRT-PCR和蛋白质免疫印迹分析检测SIRT1的mRNA和蛋白水平。通过HBV DNA的表达以及HBsAg和HBeAg的水平评估HBV复制。通过细胞计数试剂盒-8(CCK-8)和5-溴-2'-脱氧尿苷(BrdU)检测评估细胞增殖,并通过流式细胞术检测、酶联免疫吸附测定(ELISA)和caspase-3活性评估细胞凋亡。通过在线软件预测miR-1271与SIRT1之间的关系,并通过双荧光素酶报告基因检测、RNA免疫沉淀(RIP)和下拉实验进行验证。我们首先发现,在HBV相关的HCC组织和细胞中,miR-1271的表达下调而SIRT1的表达上调。miR-1271的过表达抑制了HBV相关HCC细胞中的HBV复制和细胞增殖,同时促进细胞凋亡。随后,确定SIRT1是miR-1271的靶标。此外,SIRT1的过表达逆转了miR-1271过表达对HBV相关HCC细胞中HBV复制、细胞增殖和凋亡的影响。总之,我们的研究表明,miR-1271通过靶向SIRT1抑制HBV相关HCC细胞的HBV复制和增殖并促进其凋亡,这可能有助于HBV相关HCC的诊断和治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba7e/9076187/33583b7a42ca/c9ra08248d-f1.jpg

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