WTAP-dependent N6-methyladenosine methylation of lncRNA TEX41 promotes renal cell carcinoma progression

Sci Rep. 2024 Oct 21;14(1):24742. doi: 10.1038/s41598-024-76326-9.

Abstract

The methyltransferase Wilms' tumor 1-associated protein (WTAP) has been reported to be dysregulated in various tumors. However, its role in renal cell carcinoma (RCC) remains elusive. Here, we explored whether WTAP was upregulated in RCC specimens compared to normal tissues. Functionally, WTAP promoted RCC cell proliferation and metastasis in vivo and in vitro. Mechanistically, WTAP act as an N6-methyladenosine transferase to regulate the m6A modification of long noncoding RNA TEX41. Then, the upregulated m6A modification destabilized TEX41 in a YTHDF2-dependent manner. Furthermore, TEX41 interacted with the SUZ12 protein and increased the histone methyltransferase activity of SUZ12, resulting in HDAC1 silencing. Totally, our study demonstrated the oncogenic the role of WTAP/TEX41/SUZ12/HDAC1 axis in RCC progression.

Keywords: HDAC1; Renal cell carcinoma; TEX41; WTAP.

MeSH terms

  • Adenosine* / analogs & derivatives
  • Adenosine* / metabolism
  • Animals
  • Carcinoma, Renal Cell* / genetics
  • Carcinoma, Renal Cell* / metabolism
  • Carcinoma, Renal Cell* / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Histone Deacetylase 1* / genetics
  • Histone Deacetylase 1* / metabolism
  • Humans
  • Kidney Neoplasms* / genetics
  • Kidney Neoplasms* / metabolism
  • Kidney Neoplasms* / pathology
  • Male
  • Methylation
  • Mice
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • RNA Splicing Factors / genetics
  • RNA Splicing Factors / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Adenosine
  • HDAC1 protein, human
  • Histone Deacetylase 1
  • N-methyladenosine
  • Neoplasm Proteins
  • RNA Splicing Factors
  • RNA, Long Noncoding
  • RNA-Binding Proteins
  • SUZ12 protein, human
  • Transcription Factors
  • WTAP protein, human
  • YTHDF2 protein, human