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长链非编码 RNA SNHG6 通过海绵吸附 let-7c-5p 来上调肝细胞癌中 c-Myc 的表达,起到 ceRNA 的作用。

lncRNA SNHG6 functions as a ceRNA to up-regulate c-Myc expression via sponging let-7c-5p in hepatocellular carcinoma.

机构信息

The First Department of General Surgery, Affiliated Dongguan People's Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, Guangdong, 523059, China.

出版信息

Biochem Biophys Res Commun. 2019 Nov 19;519(4):901-908. doi: 10.1016/j.bbrc.2019.09.091. Epub 2019 Sep 25.

Abstract

Emerging evidence has revealed that dysregulation of lncRNAs correlate with the development and progression of hepatocellular carcinoma (HCC). In the present study, we globally investigated the expression of SNHG6 in 31 cancer type, and we found that SNHG6 was highly expressed in various cancers, especially in HCC. High expression of SNHG6 was associated with progression and poor prognosis in patients with HCC. Gain of function and loss of function assays showed that SNHG6 promoted HCC cell proliferation. Gene Set Enrichment Analysis (GSEA) and correlation analysis suggested that SNHG6 positively correlated with c-Myc and its downstream targets. Ectopic overexpression of SNHG6 markedly increased the expression of c-Myc and its downstream targets, whereas silencing SNHG6 had the opposite effect on the expression of c-Myc and its downstream targets. Mechanistic assays revealed that SNHG6 acted as a competing endogenous RNA (ceRNA) to sponge let-7c-5p and thereby modulating the depression of c-Myc by let-7c-5p. Taken together, SNHG6 promotes HCC cell proliferation via competitively binding let-7c-5p in hepatocellular carcinoma.

摘要

越来越多的证据表明,lncRNAs 的失调与肝细胞癌 (HCC) 的发生和发展有关。在本研究中,我们全面研究了 SNHG6 在 31 种癌症类型中的表达情况,发现 SNHG6 在各种癌症中高度表达,尤其是在 HCC 中。SNHG6 的高表达与 HCC 患者的进展和预后不良相关。功能获得和功能丧失实验表明,SNHG6 促进 HCC 细胞增殖。基因集富集分析 (GSEA) 和相关性分析表明,SNHG6 与 c-Myc 及其下游靶点呈正相关。外源性过表达 SNHG6 显著增加了 c-Myc 及其下游靶点的表达,而沉默 SNHG6 则对 c-Myc 及其下游靶点的表达产生相反的影响。机制实验表明,SNHG6 作为竞争性内源性 RNA (ceRNA),可以与 let-7c-5p 结合,从而调节 let-7c-5p 对 c-Myc 的抑制作用。综上所述,SNHG6 通过在肝细胞癌中竞争性结合 let-7c-5p 促进 HCC 细胞增殖。

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