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长链非编码RNA TMPO-AS1通过海绵吸附miR-140-5p并诱导SOX4介导的上皮-间质转化促进胃癌细胞的迁移和侵袭。

Long Non-Coding RNA TMPO-AS1 Promotes Cell Migration and Invasion by Sponging miR-140-5p and Inducing SOX4-Mediated EMT in Gastric Cancer.

作者信息

Sun Yonghong, Han Chunyao

机构信息

Department of General Surgery, Second Hospital of Shanxi Medical University, Taiyuan City, Shanxi Province 030001, People's Republic of China.

出版信息

Cancer Manag Res. 2020 Feb 20;12:1261-1268. doi: 10.2147/CMAR.S235898. eCollection 2020.

Abstract

BACKGROUND

Mounting evidence show that long non-coding RNAs (lncRNAs) play critical roles in the progression of various human cancers, including gastric cancer (GC), a common gastrointestinal tumor. In this study, the biological functions of lncRNA TMPO-AS1 in GC were studied.

METHODS

TMPO-AS1 and miR-140-5p expression levels were detected in GC tissues and cell lines by RT-qPCR analysis. Knockdown or overexpression of TMPO-AS1 was conducted to evaluate the effects of TMPO-AS1 on the malignant behaviors of GC cells. Bioinformatic prediction and dual-luciferase reporter assay were performed to investigate the direct interaction between TMPO-AS1 and miR-140-5p in GC.

RESULTS

We observed that TMPO-AS1 was up-regulated in GC tissues, and high TMPO-AS1 expression in GC patients was closely correlated with aggressive clinicopathologic characteristics and poor overall survival. Functionally, gain- and loss-of-function studies showed that TMPO-AS1 overexpression enhanced the proliferation, migration, invasion and EMT of GC cells in vitro, whereas knockdown of TMPO-AS1 inhibited these malignant traits. Importantly, we demonstrated that TMPO-AS1 could function as a competing endogenous RNA (ceRNA) by sponging miR-140-5p in GC cells, thereby diminishing the inhibition on SOX4, an EMT regulator.

CONCLUSION

Our findings indicated that TMPO-AS1 promotes GC progression partly by regulating miR-140-5p/SOX4 axis, and may serve as a novel therapeutic target for GC.

摘要

背景

越来越多的证据表明,长链非编码RNA(lncRNA)在包括胃癌(GC)这种常见胃肠道肿瘤在内的多种人类癌症进展中发挥关键作用。在本研究中,我们对lncRNA TMPO-AS1在胃癌中的生物学功能进行了研究。

方法

通过RT-qPCR分析检测胃癌组织和细胞系中TMPO-AS1和miR-140-5p的表达水平。进行TMPO-AS1的敲低或过表达以评估TMPO-AS1对胃癌细胞恶性行为的影响。进行生物信息学预测和双荧光素酶报告基因检测以研究胃癌中TMPO-AS1与miR-140-5p之间的直接相互作用。

结果

我们观察到TMPO-AS1在胃癌组织中上调,胃癌患者中TMPO-AS1的高表达与侵袭性临床病理特征和较差的总生存期密切相关。在功能上,功能获得和功能丧失研究表明,TMPO-AS1过表达增强了胃癌细胞在体外的增殖、迁移、侵袭和上皮-间质转化,而TMPO-AS1的敲低则抑制了这些恶性特征。重要的是,我们证明TMPO-AS1在胃癌细胞中可通过海绵吸附miR-140-5p发挥竞争性内源RNA(ceRNA)的作用,从而减弱对EMT调节因子SOX4的抑制。

结论

我们的研究结果表明,TMPO-AS1部分通过调节miR-140-5p/SOX4轴促进胃癌进展,可能成为胃癌的一个新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/666e/7039077/1a30b6301d1a/CMAR-12-1261-g0001.jpg

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