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长链非编码 RNA RP11-436H11.5 作为竞争性内源性 RNA,通过海绵吸附 miR-335-5p 而上调 BCL-W 的表达,促进肾细胞癌的增殖和侵袭。

LncRNA RP11-436H11.5, functioning as a competitive endogenous RNA, upregulates BCL-W expression by sponging miR-335-5p and promotes proliferation and invasion in renal cell carcinoma.

机构信息

Department of Urology, Shengjing Hospital of China Medical University, Shenyang, 110004, China.

出版信息

Mol Cancer. 2017 Oct 25;16(1):166. doi: 10.1186/s12943-017-0735-3.

DOI:10.1186/s12943-017-0735-3
PMID:29070041
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5657097/
Abstract

BACKGROUND

Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play a crucial role in tumorigenesis. Here, we report a novel lncRNA, RP11-436H11.5, that regulates renal cell carcinoma (RCC) cell proliferation and invasion by sponging miR-335-5p.

METHODS

Expression of lncRNA RP11-436H11.5 was determined by a qRT-PCR assay in RCC tissues. RCC cell proliferation and invasion were measured by a cell proliferation assay and a transwell invasion assay. Expression of BCL-W was detected by a western blot assay. Interactions between lncRNA RP11-436H11.5 and miR-335-5p were measured by a luciferase reporter assay and a RNA-pull down assay. In vivo experiments were used to detect tumor formation.

RESULTS

In this study, the qRT-PCR results illustrated that lncRNA RP11-436H11.5 was more highly expressed in RCC tissues than in adjacent normal renal tissues. The results of survival analysis indicated that patients in the high lncRNA RP11-436H11.5 group presented significantly worse outcomes compared with those in the low lncRNA RP11-436H11.5 group. Downregulation of lncRNA RP11-436H11.5 suppressed RCC cell proliferation and invasion in vitro and in vivo. Luciferase reporter assay results demonstrated that lncRNA RP11-436H11.5 enhanced BCL-W expression by regulating miR-335-5p expression. LncRNA RP11-436H11.5 could function as a miR-335-5p decoy to derepress expression of BCL-W.

CONCLUSIONS

LncRNA RP11-436H11.5 could function as a competing endogenous RNA to promote RCC cell proliferation and invasion, which might serve as a therapeutic application to suppress RCC progression.

摘要

背景

越来越多的证据表明,长非编码 RNA(lncRNA)在肿瘤发生中起着至关重要的作用。在这里,我们报告了一种新的 lncRNA,RP11-436H11.5,它通过海绵 miR-335-5p 来调节肾细胞癌(RCC)细胞的增殖和侵袭。

方法

通过 qRT-PCR 检测 RP11-436H11.5 在 RCC 组织中的表达。通过细胞增殖测定和 Transwell 侵袭测定来测量 RCC 细胞的增殖和侵袭。通过 Western blot 检测 BCL-W 的表达。通过荧光素酶报告测定和 RNA 下拉测定来测量 lncRNA RP11-436H11.5 与 miR-335-5p 之间的相互作用。体内实验用于检测肿瘤形成。

结果

本研究的 qRT-PCR 结果表明,lncRNA RP11-436H11.5 在 RCC 组织中的表达高于相邻正常肾组织。生存分析结果表明,lncRNA RP11-436H11.5 高表达组患者的预后明显差于 lncRNA RP11-436H11.5 低表达组患者。体外和体内下调 lncRNA RP11-436H11.5 抑制 RCC 细胞的增殖和侵袭。荧光素酶报告测定结果表明,lncRNA RP11-436H11.5 通过调节 miR-335-5p 的表达增强 BCL-W 的表达。lncRNA RP11-436H11.5 可以作为 miR-335-5p 的诱饵来解除 BCL-W 的表达抑制。

结论

lncRNA RP11-436H11.5 可以作为竞争性内源性 RNA 促进 RCC 细胞的增殖和侵袭,这可能成为抑制 RCC 进展的治疗应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3e2/5657097/92a761b742bc/12943_2017_735_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3e2/5657097/3c38862012b6/12943_2017_735_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3e2/5657097/d3f6c8666cd2/12943_2017_735_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3e2/5657097/9ca8d1b77cd0/12943_2017_735_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3e2/5657097/470c7310c61d/12943_2017_735_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3e2/5657097/3508a6da555d/12943_2017_735_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3e2/5657097/92a761b742bc/12943_2017_735_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3e2/5657097/3c38862012b6/12943_2017_735_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3e2/5657097/d3f6c8666cd2/12943_2017_735_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3e2/5657097/9ca8d1b77cd0/12943_2017_735_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3e2/5657097/470c7310c61d/12943_2017_735_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3e2/5657097/3508a6da555d/12943_2017_735_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3e2/5657097/92a761b742bc/12943_2017_735_Fig6_HTML.jpg

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