HBV HBx-Downregulated lncRNA LINC01010 Attenuates Cell Proliferation by Interacting with Vimentin.
HBV HBx-Downregulated lncRNA LINC01010 Attenuates Cell Proliferation by Interacting with Vimentin.
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HBV HBx 下调的 lncRNA LINC01010 通过与波形蛋白相互作用来减弱细胞增殖。
DOI：
10.3390/ijms222212497
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发表时间：
2021-11-19
影响因子：
5.6
通讯作者：
Ye X
中科院分区：
文献类型：
--
作者：
Gan L;Shangguan Q;Zhang F;Tong X;Qi D;Zhao Y;Ye X
乙型肝炎病毒（Hepatitis B Virus，HBV）感染与肝细胞癌（Hepatocellular carcinoma，HCC）的发生密切相关。为了研究HBV引起HCC的机制，我们先前分析了HBV转基因细胞系HepG2 - 4D14和亲本HepG2细胞的转录，并鉴定了它们之间差异表达的长非编码RNA（lncRNA）的子集。在这项研究中，我们专注于lncRNA LINC01010，因为它在HepG2 - 4D14细胞和HCC患者的肝组织中显著下调，并与生存呈正相关。我们发现HBV编码的HBx可以减少LINC01010的转录。功能分析表明LINC01010的过表达抑制HepG2细胞的增殖、迁移和侵袭，而LINC01010的敲低促进这些过程。通过RNA免疫沉淀（RIP）和质谱分析，证实LINC01010可以与波形蛋白相互作用。进一步的研究表明，LINC01010对波形蛋白网络的延伸产生负面影响，并导致更快的亚基交换和更低的波形蛋白丝稳定性。此外，LINC01010可以减少细胞内不溶性波形蛋白的量，这表明LINC01010干扰波形蛋白聚合。这些数据表明LINC01010可以抑制波形蛋白细丝的组装。因此，我们揭示了HBV HBx下调LINC01010，LINC01010通过负调节波形蛋白丝的形成来抑制细胞增殖和迁移。总之，LINC01010是一种潜在的肿瘤抑制因子，可能抑制HBV相关的HCC发展。
Hepatitis B virus (HBV) infection is closely related to hepatocellular carcinoma (HCC) development. To investigate the mechanism of HBV causing HCC, we previously analyzed the transcription of the HBV-transgenic cell line HepG2-4D14 and parental HepG2 cells and identified a subset of long noncoding RNAs (lncRNAs) differentially expressed between them. In this study, we focus on lncRNA LINC01010, as it is significantly downregulated in HepG2-4D14 cells and in liver tissues of HCC patients, and positively correlated with survival. We found that HBV-encoded HBx can reduce the transcription of LINC01010. Functional analysis showed that the overexpression of LINC01010 inhibits proliferation, migration and invasion of HepG2 cells while the knockdown of LINC01010 promotes these processes. By taking the approach of RNA immunoprecipitation (RIP) and mass spectrometry, we identified that LINC01010 can interact with vimentin. Further studies demonstrated that LINC01010 negatively affects the vimentin network extension and causes more rapid subunit exchange and lower stability of vimentin filaments. In addition, LINC01010 can reduce the amount of insoluble vimentin within cells, which suggests that LINC01010 interfers with vimentin polymerization. These data indicate that LINC01010 can inhibit the assembly of vimentin filament. Thus, we revealed that HBV HBx-downregulated LINC01010, which suppresses cell proliferation and migration by negatively regulating the formation of vimentin filament. Taken together, LINC01010 is a potential tumor suppressor that may restrain HBV-related HCC development.
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DOI：
10.1073/pnas.1716009114
发表时间：
2017-11-14
影响因子：
11.1
作者：
Bollong, Michael J.;Pietila, Mika;Lairson, Luke L.
通讯作者：
Lairson, Luke L.
DOI：
10.1016/j.bbamcr.2020.118739
发表时间：
2020-09-01
影响因子：
5.1
作者：
Ding, Isabel;Ostrowska-Podhorodecka, Zofia;McCulloch, Christopher A.
通讯作者：
McCulloch, Christopher A.
影响因子：
5.6
作者：
Gao, Li;Lin, Peng;Chen, Gang
通讯作者：
Chen, Gang
影响因子：
13.5
作者：
Kawai, H;Suda, T;Asakura, H
通讯作者：
Asakura, H
影响因子：
4.6
作者：
Hu JJ;Song W;Zhang SD;Shen XH;Qiu XM;Wu HZ;Gong PH;Lu S;Zhao ZJ;He ML;Fan H
通讯作者：
Fan H