MicroRNA-148a-3p Directly Targets SERPINE1 to Suppress EMT-Mediated Colon Adenocarcinoma Progression

Biwen Hu; Zhenwei Chen; Xiaoguang Wang; Fei Chen; Zhengwei Song; Chenxi Cao

doi:10.2147/CMAR.S302777

MicroRNA-148a-3p Directly Targets SERPINE1 to Suppress EMT-Mediated Colon Adenocarcinoma Progression

Cancer Manag Res. 2021 Aug 11:13:6349-6362. doi: 10.2147/CMAR.S302777. eCollection 2021.

Authors

Biwen Hu^#¹, Zhenwei Chen^#¹, Xiaoguang Wang¹, Fei Chen¹, Zhengwei Song¹, Chenxi Cao¹

Affiliation

¹ Department of Surgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang Province, People's Republic of China.

^# Contributed equally.

Abstract

Aim: This research aimed at clarifying the intracellular effect of SERPINE1 in the progression of colon adenocarcinoma (COAD) and the underlying mechanism.

Methods: We obtained the expression profile of SERPINE1 in COAD via the Starbase database and verified it on COAD tissue samples through qRT-PCR and immunoblotting, respectively. Also, miRWalk, TargetScan and miRDB databases were adopted to generate the miRNA prediction that might target SERPINE1, and the gene target miR-148a-3p was confirmed using dual-luciferase assays. The effect of SERPINE1 and miR-148a-3p on COAD was further evaluated by cell experiments. MTT assay was used to detect the change of cell proliferation ability. The invasive and migratory capability of COAD cells was examined using transwell and would healing assays. Cell apoptosis was determined through flow cytometry. The expressions of genes and EMT-associated proteins were evaluated by qRT-PCR and immunoblotting. Further lucubration of the biological relevance of SERPINE1 and miR-148a-3p was conducted using rescue experiments.

Results: We found that the expression quantities of SERPINE1 in COAD tissues and cell lines were higher than those in corresponding non-cancerous tissues and normal cells. When SERPINE1 expression is reduced, EMT process is inhibited, invasion and proliferation ability of COAD cells are obviously reduced, and apoptosis level is increased. Moreover, SERPINE1 was identified as the target gene of miR-148a-3p. When the expression of miR-148a-3p was enhanced, it was found that the expression of SERPINE1 was reduced. miR-148a-3p played the similar effect of si-SERPINE1 that suppressed the COAD progression. Additionally, we found out that SERPINE1 is validated in hindering the tumor healing effect of miR148a-3p in COAD, including cell growth and invasion.

Conclusion: Our study suggests that SERPINE1/miR-148a-3p axis has potential as prognostic markers of COAD and provides reference for the development of new therapies.

Keywords: EMT; SERPINE1; colon adenocarcinoma; miR-148a-3p.