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METTL14 suppresses proliferation and metastasis of colorectal cancer by down-regulating oncogenic long non-coding RNA

Xiao Yang1,2, Sen Zhang1,2, Changyu He1

  • 1Division of Gastrointestinal and Colorectal Surgery, Ruijin Hospital, Department of General Surgery, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200001, China.

Molecular Cancer
|March 1, 2020
PubMed
Abstract

Insights

Loss of METTL14 in colorectal cancer (CRC) correlates with poor prognosis. METTL14 regulates cancer progression by affecting the m6A modification of lncRNA XIST, highlighting its role in RNA epigenetics.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cancer Research

Background:

  • N6-methyladenosine (m6A) is a key RNA epigenetic modification in eukaryotes.
  • The role of m6A in colorectal cancer (CRC) remains largely unexplored.

Purpose of the Study:

  • To investigate the clinical relevance and functional role of METTL14 in colorectal cancer.
  • To elucidate the molecular mechanisms underlying METTL14's function in CRC progression.

Main Methods:

  • Analysis of METTL14 expression in CRC patient data and tissues.
  • In vitro and in vivo gain/loss of function experiments.
  • RNA sequencing (RNA-seq), RNA pull-down, RNA immunoprecipitation (RIP), and methylated RNA immunoprecipitation (Me-RIP) assays.

Main Results:

  • Loss of METTL14 expression is associated with unfavorable prognosis in CRC patients.
  • METTL14 knockdown enhances CRC cell proliferation, invasion, tumorigenicity, and metastasis.
  • METTL14 targets lncRNA XIST, regulating its m6A modification and expression, and interacts with YTHDF2 to control XIST stability.

Conclusions:

  • METTL14 plays a crucial role in CRC progression and serves as a prognostic biomarker.
  • This study enhances the understanding of RNA epigenetics' importance in cancer biology, specifically in CRC.
Keywords:
Colorectal cancerLong non-coding RNAMETTL14RNA epigeneticsm6A

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