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在体外,敲低MIR4435-2HG通过调控miR-128-3p/MSI2轴抑制宫颈癌细胞的增殖、迁移和侵袭。

Knockdown of MIR4435-2HG Suppresses the Proliferation, Migration and Invasion of Cervical Cancer Cells via Regulating the miR-128-3p/MSI2 Axis in vitro.

作者信息

Wang Ruijing, Liu Lun, Jiao Jinwen, Gao Dongmei

机构信息

Department of Gynecology, The Affiliated Hospital of Qingdao University, Qingdao City, Shandong Province 266555, People's Republic of China.

Department of Surgery, The Affiliated Hospital of Qingdao University, Qingdao City, Shandong Province 266555, People's Republic of China.

出版信息

Cancer Manag Res. 2020 Sep 22;12:8745-8756. doi: 10.2147/CMAR.S265545. eCollection 2020.

Abstract

PURPOSE

Long non-coding RNAs (lncRNAs) play major roles in the development of several cancers, including cervical cancer (CC). The purpose of the present study is to explore the regulatory mechanism of MIR4435-2HG on CC in vitro.

PATIENTS AND METHODS

Fifty-nine pairs of CC tissues and adjacent normal tissues were collected from 59 patients by resection. The expression of lncRNA MIR4435-2HG, microRNA (miR)-128-3p and () in CC tissues and cells was detected by quantitative reverse-transcription PCR (qRT-PCR). The viability of CC cells was detected by 3-(4, 5-Dimethyl-2-Thiazolyl)-2, 5-Diphenyl-2-H-Tetrazolium Bromide (MTT) assay. The ability of migration and invasion in CC cells was measured by wound healing assay and transwell invasion assay, respectively. Starbase software and Targetscan software were utilized to predict the relationship between miR-128 and MIR4435-2HG/, respectively. The dual-luciferase reporter assay was used to confirm these interactions.

RESULTS

LncRNA MIR4435-2HG expression was significantly up-regulated in CC tissues ( < 0.001) and cells ( < 0.01). Knockdown of MIR4435-2HG inhibited the proliferation, migration and invasion of CC cells ( < 0.01). MiR-128-3p was a target of MIR4435-2HG and was negatively modulated by MIR4435-2HG ( < 0.0001, r = -0.6331). Up-regulation of miR-128-3p suppressed the proliferation, migration and invasion of CC cells ( < 0.01). In addition, was the target gene of miR-128-3p and negatively regulated by miR-128-3p ( < 0.0001, r = -0.4775). Both down-regulation of miR-128-3p and up-regulation of reversed the inhibitory effects of MIR4435-2HG knockdown on the proliferation, migration and invasion of CC cells ( < 0.05).

CONCLUSION

MIR4435-2HG knockdown suppresses the proliferation, migration and invasion of CC cells through regulating the miR-128-3p/ axis, providing a possible therapeutic strategy for CC.

摘要

目的

长链非编码RNA(lncRNA)在包括宫颈癌(CC)在内的多种癌症发生发展中起主要作用。本研究旨在探讨MIR4435 - 2HG在体外对CC的调控机制。

患者与方法

通过手术切除从59例患者中收集59对CC组织及相邻正常组织。采用定量逆转录聚合酶链反应(qRT - PCR)检测CC组织和细胞中lncRNA MIR4435 - 2HG、微小RNA(miR)- 128 - 3p及(此处原文缺失内容)的表达。采用3 -(4,5 - 二甲基 - 2 - 噻唑基)- 2,5 - 二苯基 - 2 - H - 四氮唑溴盐(MTT)法检测CC细胞的活力。分别采用伤口愈合试验和Transwell侵袭试验检测CC细胞的迁移和侵袭能力。利用Starbase软件和Targetscan软件分别预测miR - 128与MIR4435 - 2HG/(此处原文缺失内容)之间的关系。采用双荧光素酶报告基因试验验证这些相互作用。

结果

lncRNA MIR4435 - 2HG在CC组织(<0.001)和细胞(<0.01)中的表达显著上调。敲低MIR4435 - 2HG可抑制CC细胞的增殖、迁移和侵袭(<0.01)。miR - 128 - 3p是MIR4435 - 2HG的靶标,且受MIR4435 - 2HG负调控(<0.0001,r = - 0.6331)。上调miR - 128 - 3p可抑制CC细胞的增殖、迁移和侵袭(<0.01)。此外,(此处原文缺失内容)是miR - 128 - 3p的靶基因,受miR - 128 - 3p负调控(<0.0001,r = - 0.4775)。下调miR - 128 - 3p和上调(此处原文缺失内容)均逆转了敲低MIR4435 - 2HG对CC细胞增殖、迁移和侵袭的抑制作用(<0.05)。

结论

敲低MIR4435 - 2HG通过调控miR - 128 - 3p/(此处原文缺失内容)轴抑制CC细胞的增殖、迁移和侵袭,为CC提供了一种可能的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d9d/7519841/f1240267fd81/CMAR-12-8745-g0001.jpg

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