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长链非编码RNA SNHG6通过调节ETS1信号通路在非小细胞肺癌中发挥癌基因作用。

Long Noncoding RNA SNHG6 Functions as an Oncogene in Non-Small Cell Lung Cancer via Modulating ETS1 Signaling.

作者信息

Geng Hua, Li Shixiong, Xu Meilin

机构信息

Department of Pathology, Tianjin Chest Hospital, Tianjin 300222, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Jan 30;13:921-930. doi: 10.2147/OTT.S235336. eCollection 2020.

Abstract

BACKGROUND

Non-small cell lung cancer (NSCLC) is a great threat to human health and the biology of the NSCLC still remains largely unknown. Aberrantly expressed long non-coding RNA (lncRNA) Small nucleolar RNA host gene 6 (SNHG6) was involved in the tumorigenesis and progression of various cancers. The aim of this study is to investigate the roles of SNHG6 in NSCLC.

METHODS

qRT-PCR and Western blot assays were applied to detect gene expressions. Cell proliferation and migration assays were used to analyze the gene functions. Luciferase reporter assay, RNA Immunoprecipitation assay and Chromatin immunoprecipitation assay were performed to investigate the molecular mechanism.

RESULTS

We found that SNHG6 expression was significantly increased in NSCLC tissues and cell lines and its high expression was correlated with malignant features of NSCLC. In in vitro assays, knockdown of SNHG6 significantly depressed the proliferation vitality and migration activity of NSCLC cells. Research on mechanisms revealed that SNHG6 exerted its tumorigenesis role by promoting ETS1 expression via competitively binding with miR-944 and miR-181d-5p. We also demonstrated that ETS1 enhanced the expression of WIPF1 via binding to its promoter and SNHG6 could thereby regulate the expression of ETS1 target genes including WIPF1, MMP2 and MMP9.

CONCLUSION

Our study illustrates that SNHG6 is an oncogene in NSCLC and involved in NSCLC tumorigenesis by regulating ETS1 signaling via miR-944 and miR-181d-5p.

摘要

背景

非小细胞肺癌(NSCLC)对人类健康构成巨大威胁,其生物学特性仍很大程度上未知。异常表达的长链非编码RNA(lncRNA)小核仁RNA宿主基因6(SNHG6)参与了多种癌症的发生和发展。本研究旨在探讨SNHG6在NSCLC中的作用。

方法

应用qRT-PCR和蛋白质免疫印迹法检测基因表达。采用细胞增殖和迁移实验分析基因功能。进行荧光素酶报告基因实验、RNA免疫沉淀实验和染色质免疫沉淀实验以研究分子机制。

结果

我们发现SNHG6在NSCLC组织和细胞系中表达显著增加,其高表达与NSCLC的恶性特征相关。在体外实验中,敲低SNHG6显著降低了NSCLC细胞的增殖活力和迁移活性。机制研究表明,SNHG6通过与miR-944和miR-181d-5p竞争性结合来促进ETS1表达,从而发挥其致癌作用。我们还证明,ETS1通过结合其启动子增强WIPF1的表达,SNHG6进而可以调节包括WIPF1、MMP2和MMP9在内的ETS1靶基因的表达。

结论

我们的研究表明,SNHG6是NSCLC中的一个癌基因,通过miR-944和miR-181d-5p调节ETS1信号通路参与NSCLC的肿瘤发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4178/6996613/6f14c7df1bd2/OTT-13-921-g0001.jpg

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