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长链非编码RNA KCNMB2-AS1通过吸附微小RNA-374a-3p增加ROCK1表达以促进非小细胞肺癌进展。

Long Noncoding RNA KCNMB2-AS1 Increases ROCK1 Expression by Sponging microRNA-374a-3p to Facilitate the Progression of Non-Small-Cell Lung Cancer.

作者信息

Yang Haitao, Wang Ziyi, Wang Zhenyuan

机构信息

Department of Thoracic Surgery, The People's Hospital of Liaoning Province, Liaoning 110015, People's Republic of China.

Department of Thoracic Surgery, The Tenth People's Hospital of Shenyang, Liaoning 110044, People's Republic of China.

出版信息

Cancer Manag Res. 2020 Dec 11;12:12679-12695. doi: 10.2147/CMAR.S270646. eCollection 2020.

Abstract

PURPOSE

The expression and roles of most long noncoding RNAs (lncRNAs) in non-small-cell lung cancer (NSCLC) remain poorly understood. Thus, this study investigated antisense RNA 1 (KCNMB2-AS1) expression in NSCLC and determined the roles and mechanisms of in regulating NSCLC progression.

METHODS

expression in NSCLC tissues and cells was detected using reverse transcription-quantitative polymerase chain reaction. Cell proliferation, apoptosis, migration, and invasion were evaluated using Cell Counting Kit-8, flow cytometry, Transwell migration, and Transwell invasion assays, respectively. In vivo tumor xenograft models were constructed to assess tumorigenicity. Bioinformatics predictions were performed to identify microRNAs targeting . Interactions between and miR-374a-3p were analyzed using RNA immunoprecipitation, luciferase reporter, and rescue experiments.

RESULTS

levels were increased in NSCLC tissues and cells. silencing hindered NSCLC cell proliferation, migration, and invasion and promoted apoptosis in vitro. Additionally, knockdown decreased tumor growth in vivo. Mechanistically, functioned as an endogenous miR-374a-3p sponge and increased (ROCK1) expression. Furthermore, increased miR-374a-3p/ROCK1 output attenuated silencing-induced inhibition of NSCLC progression.

CONCLUSION

The KCNMB2-AS1/miR-374a-3p/ROCK1 pathway drives NSCLC progression, suggesting that this pathway can be targeted to reduce NSCLC progression.

摘要

目的

大多数长链非编码RNA(lncRNA)在非小细胞肺癌(NSCLC)中的表达及作用仍知之甚少。因此,本研究调查了非小细胞肺癌中反义RNA 1(KCNMB2-AS1)的表达,并确定了其在调节非小细胞肺癌进展中的作用及机制。

方法

采用逆转录定量聚合酶链反应检测非小细胞肺癌组织和细胞中的表达。分别使用细胞计数试剂盒-8、流式细胞术、Transwell迁移实验和Transwell侵袭实验评估细胞增殖、凋亡、迁移和侵袭。构建体内肿瘤异种移植模型以评估致瘤性。进行生物信息学预测以鉴定靶向的微小RNA。使用RNA免疫沉淀、荧光素酶报告基因和拯救实验分析与miR-374a-3p之间的相互作用。

结果

非小细胞肺癌组织和细胞中的水平升高。沉默KCNMB2-AS1可抑制非小细胞肺癌细胞的增殖、迁移和侵袭,并在体外促进细胞凋亡。此外,敲低KCNMB2-AS1可降低体内肿瘤生长。机制上,KCNMB2-AS1作为内源性miR-374a-3p海绵,增加了Rho相关卷曲螺旋蛋白激酶1(ROCK1)的表达。此外,增加的miR-374a-3p/ROCK1输出减弱了KCNMB2-AS1沉默诱导的对非小细胞肺癌进展的抑制作用。

结论

KCNMB2-AS1/miR-374a-3p/ROCK1通路驱动非小细胞肺癌进展,表明该通路可作为靶点来减少非小细胞肺癌进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ae1/7737946/4f7b65cda246/CMAR-12-12679-g0001.jpg

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