METTL3‐mediated m6A modification of pri‐miR‐148a‐3p affects prostate cancer progression by regulating TXNIP

Abstract

ObjectiveProstate cancer (PCa) severely affects men's health worldwide. The mechanism of methyltransferase‐like 3 (METTL3) in affecting PCa development by regulating miR‐148a‐3p expression via N6‐methyladenosine (m6A) modification was investigated.MethodsMETTL3, miR‐148a‐3p, and thioredoxin interacting protein (TXNIP) levels were determined using RT‐qPCR and Western blotting. The m6A modification level of miR‐148a‐3p was observed by Me‐RIP assay. Bioinformatics website predicted miR‐148a‐3p and TXNIP levels in PCa and their correlation, and the binding site between them was verified by dual‐luciferase assay. The proliferation, migration, invasion, and apoptosis of PCa cells were examined by CCK‐8 assay, Transwell assay, and flow cytometry. A transplanted tumor model was established in nude mice to observe the tumor growth ability, followed by determination of TXNIP levels in tumor tissues by immunohistochemistry.ResultsMETTL3 interference restrained the proliferation, migration, and invasion and promoted apoptosis of PCa cells. METTL3 up‐regulated miR‐148a‐3p by promoting the m6A modification of pri‐miR‐148a‐3p in PCa cells. miR‐148a‐3p overexpression nullified the inhibitory actions of silencing METTL3 on PCa cell growth. miR‐148a‐3p facilitated PCa cell growth by silencing TXNIP. METTL3 interference inhibited tumor growth by down‐regulating miR‐148a‐3p and up‐regulating TXNIP.ConclusionMETTL3 promoted miR‐148a‐3p by mediating the m6A modification of pri‐miR‐148a‐3p, thereby targeting TXNIP, interfering with METTL3 to inhibit the proliferation, migration and invasion of PCa cells, promote apoptosis, and inhibit tumor growth in nude mice.

Evaluation of miR-148a-3p and miR-106a-5p as Biomarkers for Prostate Cancer: Pilot Study

“…Li G et al illustrated the role of miR-148a-3p in PCa development. Methiltransferase-like 3 (METTL3) promoted by miR-146a-3p favors apoptosis and inhibits prostate tumor growth in nude mice [41]. MiR-146a-3p may target reticulon-4 (RTN4) in PCa tissues and cell lines.…”