METTL14 promotes prostate tumorigenesis by inhibiting THBS1 via an m6A-YTHDF2-dependent mechanism

Area of Science:

• Oncology
• Epigenetics
• Molecular Biology

Background:

• N6-methyladenine (m6A) is a key RNA modification implicated in various cancers.
• The specific role of m6A regulators in prostate cancer (PCa) remains largely unexplored.
• METTL14, an m6A writer, is increasingly recognized for its potential involvement in tumorigenesis.

Purpose of the Study:

• To investigate the role and mechanism of METTL14 in prostate cancer (PCa).
• To determine if METTL14 expression correlates with patient prognosis.
• To identify downstream targets of METTL14 in PCa.

Main Methods:

• Quantitative analysis of METTL14 expression in PCa tissues.
• In vitro and in vivo functional assays to assess the impact of METTL14 knockdown on tumor proliferation.
• RNA sequencing (RNA-seq) and m6A-specific immunoprecipitation followed by sequencing (MeRIP-seq) to identify direct targets.
• Western blot analysis to confirm protein expression levels.

Main Results:

• METTL14 expression was significantly upregulated in PCa and correlated with poor patient prognosis.
• Knockdown of METTL14 inhibited PCa cell proliferation in vitro and tumor growth in vivo.
• THBS1 was identified as a direct downstream target of METTL14.
• METTL14 mediated the downregulation of THBS1 expression through an m6A-dependent mechanism, involving YTHDF2-mediated mRNA degradation.

Conclusions:

• METTL14 functions as an oncogene in PCa by suppressing THBS1 expression via the m6A-YTHDF2 pathway.
• METTL14 represents a potential prognostic biomarker for PCa.
• Targeting METTL14 may offer a novel therapeutic strategy for prostate cancer.