METTL3 promotes prostate cancer progression by regulating miR-182 maturation in m6A-dependent manner

Dawei Wang1, Xiaojing Wang1, Baoxing Huang1

  • 1Department of Urology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Andrologia
|April 12, 2022
PubMed

Insights

Methyltransferase-like 3 (METTL3) promotes prostate cancer progression by regulating m6A modification of pre-miR-182. Inhibiting METTL3 may offer a new targeted therapy for prostate cancer (PCa).

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Methyltransferase-like 3 (METTL3) is involved in RNA modification and cancer progression.
  • METTL3's role in prostate cancer (PCa) via N6-methyladenosine (m6A) modification of non-coding RNA remains unclear.

Purpose of the Study:

  • To investigate the role of METTL3 in prostate cancer (PCa) development.
  • To elucidate the mechanism by which METTL3 promotes PCa, focusing on m6A modification of non-coding RNAs.

Main Methods:

  • Quantitative reverse transcription PCR (qRT-PCR) and Western blot to analyze METTL3 expression.
  • Cell proliferation, migration, invasion, and tumorigenesis assays (CCK-8, colony formation, wound-healing, Transwell, and nude mice models).
  • N6-methyladenosine (m6A) RNA immunoprecipitation (MeRIP) and co-immunoprecipitation assays to determine molecular interactions and RNA modification.

Main Results:

  • METTL3 is highly expressed in PCa tissues and cells.
  • METTL3 knockdown inhibited PCa cell proliferation, migration, invasion, and tumorigenesis; conversely, overexpression promoted these processes.
  • METTL3 upregulates m6A levels, interacts with DGCR8, and regulates the maturation of pre-miR-182, thereby promoting PCa progression.

Conclusions:

  • METTL3 promotes prostate cancer (PCa) progression through the m6A modification and maturation of pre-miR-182.
  • METTL3 is a potential therapeutic target for PCa treatment.

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