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HBx 通过抑制 miR-187-5p 的转录水平促进肝细胞癌的进展。

HBx promotes hepatocellular carcinoma progression by repressing the transcription level of miR-187-5p.

机构信息

College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan 430081, China.

Hubei Institute of Blood Transfusion, Wuhan Blood Center, Wuhan 430033, China.

出版信息

Aging (Albany NY). 2023 Aug 1;15(15):7533-7550. doi: 10.18632/aging.204921.

DOI:10.18632/aging.204921
PMID:37531206
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10457053/
Abstract

HBV-associated hepatitis B virus x protein (HBx) plays multiple roles in the development of hepatocellular carcinoma. In our prior study, we discovered that miR-187-5p expression was inhibited by HBx. To investigate the underlying molecular mechanism of HBx-mediated miR-187-5p downregulation in hepatocellular carcinoma cells, effects of HBx and miR-187-5p on hepatoma carcinoma cell were observed, as well as their interactions. Through and experiments, we demonstrated that overexpression of miR-187-5p inhibited proliferation, migration, and invasion. Simultaneously, we observed a dysregulation in the expression of miR-187-5p in liver cancer cell lines, which may be attributed to transcriptional inhibition through the E2F1/FoxP3 axis. Additionally, we noted that HBx protein is capable of enhancing the expression of E2F1, a transcription factor that promotes the expression of FoxP3. In conclusion, our results suggest that the inhibitory effect of HBx on miR-187-5p is mediated through the E2F1/FoxP3 axis. As shown in this work, HBx promotes hepatoma carcinoma cell proliferation, migration, and invasion through the E2F1/FoxP3/miR-187 axis. It provides a theoretical basis for finding therapeutic targets that will help clinic treatment for HCC.

摘要

HBV 相关的乙型肝炎病毒 x 蛋白(HBx)在肝细胞癌的发展中发挥多种作用。在我们之前的研究中,我们发现 miR-187-5p 的表达受到 HBx 的抑制。为了研究 HBx 介导的 miR-187-5p 在肝癌细胞中下调的潜在分子机制,观察了 HBx 和 miR-187-5p 对肝癌细胞的影响及其相互作用。通过 和 实验,我们证明了 miR-187-5p 的过表达抑制了增殖、迁移和侵袭。同时,我们观察到肝癌细胞系中 miR-187-5p 的表达失调,这可能归因于通过 E2F1/FoxP3 轴的转录抑制。此外,我们注意到 HBx 蛋白能够增强转录因子 E2F1 的表达,E2F1 促进 FoxP3 的表达。总之,我们的结果表明,HBx 对 miR-187-5p 的抑制作用是通过 E2F1/FoxP3 轴介导的。如本工作所示,HBx 通过 E2F1/FoxP3/miR-187 轴促进肝癌细胞的增殖、迁移和侵袭。它为寻找治疗靶点提供了理论依据,有助于 HCC 的临床治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b696/10457053/b151659b763f/aging-15-204921-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b696/10457053/5f0a9ff25234/aging-15-204921-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b696/10457053/b151659b763f/aging-15-204921-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b696/10457053/34d1742fa68d/aging-15-204921-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b696/10457053/726a1a5eaa74/aging-15-204921-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b696/10457053/b151659b763f/aging-15-204921-g008.jpg

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