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长链非编码 RNA XIST 作为 miR-194-5p 的分子海绵调节肝癌细胞中 MAPK1 的表达。

LncRNA XIST functions as a molecular sponge of miR-194-5p to regulate MAPK1 expression in hepatocellular carcinoma cell.

机构信息

Department of Emergency Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.

Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.

出版信息

J Cell Biochem. 2018 Jun;119(6):4458-4468. doi: 10.1002/jcb.26540. Epub 2018 Feb 28.

Abstract

Increasing evidence highlights the important role of XIST, a long non-coding RNA (lncRNA), in the regulation of multiple cancers. However, the underlying mechanism of XIST in human hepatocellular carcinoma (HCC) still remains to be explored. Herein, intended to investigate the functional role of XIST in HCC initiation and progression. We first detected that XIST was significantly upregulated in HCC tissues and associated with tumor size and vascular invasion. Gain- and loss-of-function of XIST further presented that XIST promoted the progression of HCC cells, including proliferation, migration, and invasion. Moreover, silencing of XIST could inhibit tumor growth in vivo. We also found that XIST could target miR-194-5p and thus decrease miR-194-5p expression. Besides that, restoring XIST could reverse the inhibitory effect of miR-194-5p on the proliferation and invasion of HCC cells. We further elucidated such rescue role might through derepressing MAPK1 expression, the target of miR-194-5p. In brief, the above results elucidate the important role of XIST in HCC tumorigenesis, suggesting that XIST might be a candidate prognostic biomarker and a novel therapeutic target for treating HCC.

摘要

越来越多的证据强调了 XIST(一种长链非编码 RNA(lncRNA))在多种癌症的调控中的重要作用。然而,XIST 在人肝细胞癌(HCC)中的潜在机制仍有待探索。在此,旨在研究 XIST 在 HCC 发生和进展中的功能作用。我们首先检测到 XIST 在 HCC 组织中显著上调,并与肿瘤大小和血管侵犯相关。XIST 的增益和损耗功能进一步表明,XIST 促进了 HCC 细胞的进展,包括增殖、迁移和侵袭。此外,沉默 XIST 可以抑制体内肿瘤生长。我们还发现 XIST 可以靶向 miR-194-5p,从而降低 miR-194-5p 的表达。除此之外,恢复 XIST 可以逆转 miR-194-5p 对 HCC 细胞增殖和侵袭的抑制作用。我们进一步阐明了这种挽救作用可能是通过去抑制 miR-194-5p 的靶基因 MAPK1 的表达来实现的。总之,上述结果阐明了 XIST 在 HCC 肿瘤发生中的重要作用,表明 XIST 可能是 HCC 预后的候选生物标志物和治疗靶点。

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