Cancer Management and Research (Sep 2020)
Knockdown of MIR4435-2HG Suppresses the Proliferation, Migration and Invasion of Cervical Cancer Cells via Regulating the miR-128-3p/MSI2 Axis in vitro
Abstract
Ruijing Wang,1 Lun Liu,2 Jinwen Jiao,1 Dongmei Gao1 1Department of Gynecology, The Affiliated Hospital of Qingdao University, Qingdao City, Shandong Province 266555, People’s Republic of China; 2Department of Surgery, The Affiliated Hospital of Qingdao University, Qingdao City, Shandong Province 266555, People’s Republic of ChinaCorrespondence: Dongmei GaoDepartment of Gynecology, The Affiliated Hospital of Qingdao University, Qingdao City, Shandong Province 266555, People’s Republic of ChinaTel +86- 0532- 82919505Email [email protected]: 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 Musashi 2 (MSI2) 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/MSI2, respectively. The dual-luciferase reporter assay was used to confirm these interactions.Results: LncRNA MIR4435-2HG expression was significantly up-regulated in CC tissues (P < 0.001) and cells (P < 0.01). Knockdown of MIR4435-2HG inhibited the proliferation, migration and invasion of CC cells (P < 0.01). MiR-128-3p was a target of MIR4435-2HG and was negatively modulated by MIR4435-2HG (P < 0.0001, r = − 0.6331). Up-regulation of miR-128-3p suppressed the proliferation, migration and invasion of CC cells (P < 0.01). In addition, MSI2 was the target gene of miR-128-3p and negatively regulated by miR-128-3p (P < 0.0001, r = − 0.4775). Both down-regulation of miR-128-3p and up-regulation of MSI2 reversed the inhibitory effects of MIR4435-2HG knockdown on the proliferation, migration and invasion of CC cells (P < 0.05).Conclusion: MIR4435-2HG knockdown suppresses the proliferation, migration and invasion of CC cells through regulating the miR-128-3p/MSI2 axis, providing a possible therapeutic strategy for CC.Keywords: cervical cancer, lncRNA MIR4435-2HG, miR-128-3p, MSI2
