N6-methyladenosine demethylase ALKBH5 suppresses colorectal cancer progression potentially by decreasing PHF20 mRNA methylation
Zhen Zhang, Ling Wang, Long Zhao, Quan Wang, Changjiang Yang, Mengmeng Zhang, Bo Wang, Kewei Jiang, Yingjiang Ye, Shan Wang, Zhanlong Shen (2022) N6-methyladenosine demethylase ALKBH5 suppresses colorectal cancer progression potentially by decreasing PHF20 mRNA methylation Clin Transl Med (IF: 6.8) 12(8) e940
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Abstract
As the most widespread mRNAs modification, N6-methyladenosine (m6 A) is dynamically and reversibly modulated by methyltransferases and demethylases. ALKBH5 is a major demethylase, and plays vital roles in the progression of cancers. However, the role and mechanisms of ALKBH5 in colorectal cancer (CRC) is unclear.Herein, we discovered that in CRC, downregulated ALKBH5 was closely related to poor prognosis of CRC patients. Functionally, our results demonstrated that knockdown of ALKBH5 enhanced the proliferation, migration and invasion of LOVO and RKO in vitro, while overexpression of ALKBH5 inhibited the functions of these cells. The results also demonstrated that knockdown of ALKBH5 promoted subcutaneous tumorigenesis of LOVO in vivo, while overexpression of ALKBH5 suppressed this ability. Mechanistically, results from joint analyses of MeRIP-seq and RNA-seq indicated that PHF20 mRNA was a key molecule that was regulated by ALKBH5-mediated m6 A modification. Further experiments indicated that ALKBH5 may inhibit stability of PHF20 mRNA by removing the m6 A modification of PHF20 mRNA 3'UTR.ALKBH5 suppresses CRC progression by decreasing PHF20 mRNA methylation. ALKBH5-mediated m6 A modification of PHF20 mRNA can serve as a hopeful strategy for the intervention and treatment of CRC.© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.
Links
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9386323http://www.ncbi.nlm.nih.gov/pubmed/35979628
http://dx.doi.org/10.1002/ctm2.940
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