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长链非编码 RNA SNHG6 通过调控 miR-26a-5p/MAPK6 促进乳腺癌细胞增殖、迁移和侵袭。

Long non-coding RNA SNHG6 enhances cell proliferation, migration and invasion by regulating miR-26a-5p/MAPK6 in breast cancer.

机构信息

Department of breast surgery, The first affiliated hospital of Zhengzhou University, Zhengzhou City, Henan Province, China.

Department of breast surgery, The first affiliated hospital of Zhengzhou University, Zhengzhou City, Henan Province, China.

出版信息

Biomed Pharmacother. 2019 Feb;110:294-301. doi: 10.1016/j.biopha.2018.11.016. Epub 2018 Dec 3.

DOI:10.1016/j.biopha.2018.11.016
PMID:30522015
Abstract

The long non-coding RNA (lncRNA) has recently been shown to be important regulators involved in the progression of various human cancers. Small nucleolar RNA host gene 6 (SNHG6) is a recently identified cancer-related lncRNA. However, the clinical significance and biological function of SNHG6 in breast cancer (BC) are still unclear. In the present study, we found that SNHG6 was highly expressed in BC tissues and cell lines, which was associated with poorer clinicopathologic features. Knockdown of SNHG6 inhibited BC cell proliferation, migration and invasion in vitro and in vivo using CCK-8, Edu staining, transwell assays and nude mice model. Moreover, bioinformatics analysis and luciferase reporter experiments indicated that SNHG6 serves as an endogenous sponge by directly binding to miR-26a-5p and down-regulating miR-26a-5p expression. MiR-26a-5p overexpression significantly enhanced the effect of SNHG6 knockdown on the cell behaviors in BC. Furthermore, bioinformatics analysis and luciferase reporter indicated that MAPK6 was validated as a target of miR-26a-5p. Therefore, our study may reveal a novel SNHG6/miR-26a-5p/MAPK6 pathway regulatory axis in BC pathogenesis. SNHG6 may serve as a potential prognostic and therapeutic target in the treatment of BC.

摘要

长链非编码 RNA(lncRNA)最近被证明是参与各种人类癌症进展的重要调节因子。小核仁 RNA 宿主基因 6(SNHG6)是最近发现的与癌症相关的 lncRNA。然而,SNHG6 在乳腺癌(BC)中的临床意义和生物学功能尚不清楚。在本研究中,我们发现 SNHG6 在 BC 组织和细胞系中高表达,与较差的临床病理特征相关。通过 CCK-8、Edu 染色、transwell 测定和裸鼠模型,敲低 SNHG6 抑制了 BC 细胞的体外和体内增殖、迁移和侵袭。此外,生物信息学分析和荧光素酶报告实验表明,SNHG6 通过直接结合 miR-26a-5p 并下调 miR-26a-5p 的表达,作为一种内源性海绵体发挥作用。miR-26a-5p 的过表达显著增强了 SNHG6 敲低对 BC 细胞行为的影响。此外,生物信息学分析和荧光素酶报告表明,MAPK6 被验证为 miR-26a-5p 的靶标。因此,我们的研究可能揭示了 BC 发病机制中一种新的 SNHG6/miR-26a-5p/MAPK6 通路调节轴。SNHG6 可能作为 BC 治疗中潜在的预后和治疗靶点。

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