MCM3AP-AS1/miR-876-5p/WNT5A axis regulates the proliferation of prostate cancer cells

Li Zhang,Yalin Lv,Jie Wu,Yujun Li,Yuwei Zou,Lili Wang,Mengqi Sun,Yanxia Jiang,Xiangyan Zhang,Jin Xu

doi:10.1186/s12935-020-01365-x

Abstract

BackgroundAlthough the fact that long non-coding RNA MCM3AP antisense RNA 1 (MCM3AP-AS1) is oncogenic in several cancers is well documented, very few researchers investigate its expression and function in prostate cancer.MethodsPaired prostate cancer samples were selected, and expressions of MCM3AP-AS1, miR-876-5p and WNT5A were examined by qRT-PCR. MCM3AP-AS1 shRNA was transfected into LNCaP and PC-3 cell lines, and then the proliferative activity and apoptosis of cancer cells were detected by CCK-8 assay, EdU assay and flow cytometry analysis, respectively. qRT-PCR and Western blot were used to analyze the changes of miR-876-5p and WNT5A. Luciferase reporter gene assay was employed to determine the regulatory relationship between miR-876-5p and MCM3AP-AS1, miR-876-5p and WNT5A.ResultsMCM3AP-AS1 was significantly up-regulated in cancerous tissues of prostate cancer samples, positively correlated with the expression of WNT5A, while negatively related with miR-876-5p. After transfection of MCM3AP-AS1 shRNA into prostate cancer cells, the proliferative ability of cancer cells was signally inhibited, but the apoptosis of cancer cells was increased. MCM3AP-AS1 shRNA could reduce the expression of WNT5A on both mRNA and protein levels. Besides, MCM3AP-AS1 was identified as a sponge of miR-876-5p. WNT5A was validated as a target gene of miR- 876-5p.ConclusionMCM3AP-AS1 is abnormally up-regulated in prostate cancer tissues and can modulate the proliferation and apoptosis of prostate cancer cells, which has the potential to be the “ceRNA” to regulate the expression of WNT5A by targeting miR-876-5p.

Highlights

Prostate cancer (PCa) is labeled as one of the most prevailing tumors among male patients, with the morbidity and mortality of PCa worldwide accounting for 7.1/105 and 3.8/105 in 2018, respectively [1]
MCM3AP‐AS1 was up‐regulated in PCa and predicted a poor prognosis First of all, we examined the expressions of MCM3APAS1 in PCa tissues and PCa cell lines by qRT-PCR
In The Cancer Genome Atlas (TCGA) data, the expression of MCM3AP-AS1 in PCa was higher than normal tissue according to the GEPIA database (The red column is the cancerous tissue, and the gray column is the adjacent tissue) (Additional file 1: Figure S1)

Summary

Introduction

Prostate cancer (PCa) is labeled as one of the most prevailing tumors among male patients, with the morbidity and mortality of PCa worldwide accounting for 7.1/105 and 3.8/105 in 2018, respectively [1]. Long non-coding RNA (lncRNA), a group of non-coding RNA (ncRNA), whose length is over 200 bp, lacks open reading frame and does not have complete protein coding function [5]. Accumulating research validates that lncRNAs can affect the progression of many tumors [8, 9]. LncRNA micro-chromosome maintenance protein 3-associated protein antisense RNA 1 (MCM3AP-AS1) is reported to play an important role in the progression of several kinds of cancers. Up-regulation of MCM3AP-AS1 expression in hepatocellular carcinoma and glioblastoma can promote malignant phenotypes of cancer cells [10, 11]. The fact that long non-coding RNA MCM3AP antisense RNA 1 (MCM3AP-AS1) is oncogenic in several cancers is well documented, very few researchers investigate its expression and function in prostate cancer

Methods

Results

Conclusion