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

Guoqiang Li1, Junwen Liu2, Yinhuai Wang1

  • 1Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, China.

PubMed
Abstract

Insights

Methyltransferase-like 3 (METTL3) promotes prostate cancer (PCa) by upregulating miR-148a-3p via m6A modification, which silences TXNIP. Interfering with METTL3 inhibits PCa progression and tumor growth.

Area of Science:

  • Molecular Oncology
  • Epigenetics
  • RNA Modifications

Background:

  • Prostate cancer (PCa) is a significant global health concern for men.
  • The role of methyltransferase-like 3 (METTL3) in PCa pathogenesis requires elucidation.
  • N6-methyladenosine (m6A) modification is increasingly recognized for its role in cancer.

Purpose of the Study:

  • To investigate the mechanism by which METTL3 influences PCa development.
  • To determine the regulatory relationship between METTL3, miR-148a-3p, and TXNIP in PCa.
  • To explore the potential of targeting the METTL3/miR-148a-3p/TXNIP axis for PCa therapy.

Main Methods:

  • Quantitative real-time PCR (RT-qPCR) and Western blotting assessed gene and protein expression.
  • Me-RIP assay quantified m6A modification levels of pri-miR-148a-3p.
  • In vitro (cell-based assays) and in vivo (xenograft mouse models) experiments evaluated PCa cell behavior and tumor growth.

Main Results:

  • METTL3 interference suppressed PCa cell proliferation, migration, and invasion, while promoting apoptosis.
  • METTL3 upregulated miR-148a-3p expression through m6A modification of pri-miR-148a-3p.
  • miR-148a-3p overexpression reversed the inhibitory effects of METTL3 silencing; miR-148a-3p silenced TXNIP, promoting PCa cell growth.

Conclusions:

  • METTL3 promotes PCa progression by enhancing miR-148a-3p via m6A modification, leading to TXNIP downregulation.
  • Targeting METTL3 effectively inhibits PCa cell proliferation, migration, invasion, and tumor growth in vivo.
  • The METTL3/miR-148a-3p/TXNIP pathway represents a potential therapeutic target for prostate cancer.

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