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miRNA Expression Analyses in Prostate Cancer Clinical Tissues
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m6A methyltransferase METTL3 promotes the progression of prostate cancer via m6A-modified LEF1

X-X Ma1, Z-G Cao, S-L Zhao

  • 1Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China. 13645193123@163.com.

European Review for Medical and Pharmacological Sciences
|April 25, 2020
PubMed
Abstract

Insights

METTL3 promotes prostate cancer (PCa) progression by methylating LEF1 mRNA, activating the Wnt pathway. This finding highlights METTL3 as a potential therapeutic target for PCa.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Prostate cancer (PCa) remains a significant health concern with complex regulatory mechanisms.
  • N6-Methyladenosine (m6A) methylation is increasingly recognized for its role in cancer development.
  • The methyltransferase METTL3 and its downstream targets are implicated in various cancers.

Purpose of the Study:

  • To investigate the role of METTL3 in prostate cancer progression.
  • To elucidate the regulatory effect of METTL3 on LEF1 mRNA through m6A methylation.
  • To determine the impact of the METTL3/LEF1 axis on the Wnt pathway and cell migration in PCa.

Main Methods:

  • Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Spearman correlation analysis on PCa tissues.
  • Kaplan-Meier survival analysis for METTL3-affected patients.
  • Wound closure assays, Western blotting, and TOP/FOP-Flash assays in PC-3 cells.
  • RNA-Binding Protein Immunoprecipitation (RIP) assays to confirm molecular interactions.

Main Results:

  • METTL3 and LEF1 were significantly upregulated in PCa tissues, correlating positively with each other.
  • High METTL3 levels predicted poor prognosis in PCa patients.
  • METTL3 knockdown reduced PCa cell migration, downregulated LEF1 protein, and inhibited Wnt pathway activity.
  • RIP assays confirmed m6A methylation sites on LEF1 mRNA and interaction with METTL3 and IGF2BP2.
  • LEF1 overexpression partially rescued the effects of METTL3 knockdown.

Conclusions:

  • METTL3 is upregulated in PCa and promotes cancer progression.
  • METTL3 facilitates PCa progression by mediating m6A methylation of LEF1 mRNA, thereby activating the Wnt pathway.
  • The METTL3/LEF1 axis represents a key regulatory mechanism in prostate cancer development.

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