WTAP regulates autophagy in colon cancer cells by inhibiting FLNA through N6-methyladenosine

Cell Adh Migr. 2023 Dec;17(1):1-13. doi: 10.1080/19336918.2023.2180196.

Abstract

Our study investigated the role of WTAP in colon cancer. We employed experiments including m6A dot blot hybridization, methylated RNA immunoprecipitation, dual-luciferase, and RNA immunoprecipitation to investigate the regulatory mechanism of WTAP. Western blot was performed to analyze the expression of WTAP, FLNA and autophagy-related proteins in cells. Our results confirmed the up-regulation of WTAP in colon cancer and its promoting effect on proliferation and inhibiting effect on apoptosis. FLNA was the downstream gene of WTAP and WTAP-regulated m6A modification led to post-transcriptional repression of FLNA. The rescue experiments showed that WTAP/FLNA could inhibit autophagy. WTAP-mediated m6A modification was confirmed to be crucial in colon cancer development, providing new insights into colon cancer therapy.

Keywords: FLNA; WTAP; autophagy; colon cancer; m6A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Autophagy
  • Cell Cycle Proteins
  • Colonic Neoplasms*
  • Filamins
  • Humans
  • RNA
  • RNA Splicing Factors

Substances

  • RNA
  • WTAP protein, human
  • RNA Splicing Factors
  • Cell Cycle Proteins
  • FLNA protein, human
  • Filamins

Grants and funding

This study was supported in part by grants from Scientific Research Project of Taizhou Science and Technology Bureau in Zhejiang Province (NO. 20ywa47) and Health science and Technology Project of Zhejiang Province (2020RC143). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.