Open AccessN6‐methyladenosine demethylase ALKBH5 suppresses colorectal cancer progression potentially by decreasing PHF20 mRNA methylation
Author(s) -
Zhang Zhen,
Wang Ling,
Zhao Long,
Wang Quan,
Yang Changjiang,
Zhang Mengmeng,
Wang Bo,
Jiang Kewei,
Ye Yingjiang,
Wang Shan,
Shen Zhanlong
Publication year - 2022
Publication title -
clinical and translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
H-Index - 1
ISSN - 2001-1326
DOI - 10.1002/ctm2.940
Subject(s) - demethylase , gene knockdown , biology , messenger rna , n6 methyladenosine , methyltransferase , colorectal cancer , cancer research , carcinogenesis , methylation , rna methylation , cancer , epigenetics , gene , biochemistry , genetics
Background As the most widespread mRNAs modification, N6‐methyladenosine (m 6 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. Results 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 m 6 A modification. Further experiments indicated that ALKBH5 may inhibit stability of PHF20 mRNA by removing the m 6 A modification of PHF20 mRNA 3′UTR. Conclusions ALKBH5 suppresses CRC progression by decreasing PHF20 mRNA methylation. ALKBH5‐mediated m 6 A modification of PHF20 mRNA can serve as a hopeful strategy for the intervention and treatment of CRC.