Hepatitis B virus induces cell proliferation via HBx-induced microRNA-21 in hepatocellular carcinoma by targeting programmed cell death protein4 (PDCD4) and phosphatase and tensin homologue (PTEN).
Hepatitis B virus induces cell proliferation via HBx-induced microRNA-21 in hepatocellular carcinoma by targeting programmed cell death protein4 (PDCD4) and phosphatase and tensin homologue (PTEN).
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DOI：
10.1371/journal.pone.0091745
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Venugopal SK
中科院分区：
文献类型：
--
作者：
Damania P;Sen B;Dar SB;Kumar S;Kumari A;Gupta E;Sarin SK;Venugopal SK
B型肝炎病毒感染诱发的肝细胞癌是发展中国家面临的主要问题之一。HBV蛋白之一HBx通过几种机制调节宿主细胞机器。在这项研究中，我们假设HBV通过HBx诱导的microRNA-21在肝细胞癌中增强细胞增殖。Huh 7和Hep G2细胞中HBx基因过表达，并检测miRNA-21表达和细胞增殖。miRNA-21在这些细胞中过表达，分析细胞增殖和靶蛋白。为了证实miRNA-21在HBx诱导的增殖中的作用，将Hep G 2.2.1.5细胞（稳定表达HBV的细胞系）用于miRNA-21抑制研究。HBx过表达分别增强Huh 7和Hep G2细胞的增殖（增加3.7和4.5倍; n = 3; p<0.01）和miRNA-21表达（增加24和36倍，用5S rRNA标准化; p<0.001）。 HBx还导致miRNA-21靶蛋白、PDCD 4和PTEN的抑制。miRNA-21导致增殖显著增加（相对于对照细胞增加2倍和2.3倍;在Huh 7和Hep G2细胞中分别为p<0.05），并降低靶蛋白、PDCD 4和PTEN表达。抗miR-21导致增殖显著降低（p<0.05）并增加miRNA-21靶蛋白表达。我们的结论是，HBV感染增强细胞增殖，至少部分，通过HBx诱导的miRNA-21表达在肝细胞癌的进展。
Hepatitis B viral infection-induced hepatocellular carcinoma is one of the major problems in the developing countries. One of the HBV proteins, HBx, modulates the host cell machinery via several mechanisms. In this study we hypothesized that HBV enhances cell proliferation via HBx-induced microRNA-21 in hepatocellular carcinoma. HBx gene was over-expressed, and miRNA-21 expression and cell proliferation were measured in Huh 7 and Hep G2 cells. miRNA-21 was over-expressed in these cells, cell proliferation and the target proteins were analyzed. To confirm the role of miRNA-21 in HBx-induced proliferation, Hep G 2.2.1.5 cells (a cell line that expresses HBV stably) were used for miRNA-21 inhibition studies. HBx over-expression enhanced proliferation (3.7- and 4.5-fold increase; n = 3; p<0.01) and miRNA-21 expression (24- and 36-fold increase, normalized with 5S rRNA; p<0.001) in Huh 7 and Hep G2 cells respectively. HBx also resulted in the inhibition of miRNA-21 target proteins, PDCD4 and PTEN. miRNA-21 resulted in a significant increase in proliferation (2- and 2.3-fold increase over control cells; p<0.05 in Huh 7 and Hep G2 cells respectively) and decreased target proteins, PDCD4 and PTEN expression. Anti-miR-21 resulted in a significant decrease in proliferation (p<0.05) and increased miRNA-21 target protein expression. We conclude that HBV infection enhances cell proliferation, at least in part, via HBx-induced miRNA-21 expression during hepatocellular carcinoma progression.
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10.1152/ajpgi.00220.2009
发表时间：
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作者：
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Zern, Mark A.