1. Academic Validation
  2. METTL14 promotes prostate tumorigenesis by inhibiting THBS1 via an m6A-YTHDF2-dependent mechanism

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

  • Cell Death Discov. 2022 Mar 30;8(1):143. doi: 10.1038/s41420-022-00939-0.
Yongjie Wang  # 1 Junfei Chen  # 2 Wei-Qiang Gao 3 4 Ru Yang 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Oncogenes and Related Genes, Renji-MedX Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 200127, Shanghai, China.
  • 2 State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 200032, Shanghai, China.
  • 3 State Key Laboratory of Oncogenes and Related Genes, Renji-MedX Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 200127, Shanghai, China. gao.weiqiang@sjtu.edu.cn.
  • 4 School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, 200030, Shanghai, China. gao.weiqiang@sjtu.edu.cn.
  • 5 State Key Laboratory of Oncogenes and Related Genes, Renji-MedX Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 200127, Shanghai, China. yangruchina@qq.com.
  • # Contributed equally.
Abstract

N6-methyladenine (m6A) is the most predominant RNA modification, which has been shown to be related to many types of cancers. However, understanding of its role in prostate Cancer (PCa) is largely unknown. Here, we report an upregulation of METTL14 that was correlated with poor prognosis in PCa patients. Functionally, knocking down METTL14 inhibited tumor proliferation both in vitro and in vivo. Mechanically, RNA-seq and MeRIP-seq analyses identified THBS1 as the downstream target of METTL14 in PCa. METTL14 downregulated THBS1 expression in an m6A-dependent manner, which resulted in the recruitment of YTHDF2 to recognize and degrade Thrombospondin 1 (THBS1) mRNA. Thus, our findings revealed that METTL14 acted as an oncogene by inhibiting THBS1 expression via an m6A-YTHDF2-dependent manner. METTL14 could be a potential prognosis marker and a therapeutic target.

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