N6-methyladenosine demethylase ALKBH5 suppresses colorectal cancer progression potentially by decreasing PHF20 mRNA methylation.
N6-methyladenosine demethylase ALKBH5 suppresses colorectal cancer progression potentially by decreasing PHF20 mRNA methylation.
复制标题
N6-甲基腺苷去甲基化酶 ALKBH5 通过降低 PHF20 mRNA 甲基化来潜在抑制结直肠癌进展。
DOI：
10.1002/ctm2.940
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发表时间：
2022-08
影响因子：
10.6
通讯作者：
Shen, Zhanlong
中科院分区：
文献类型：
--
作者：
Zhang, Zhen;Wang, Ling;Zhao, Long;Wang, Quan;Yang, Changjiang;Zhang, Mengmeng;Wang, Bo;Jiang, Kewei;Ye, Yingjiang;Wang, Shan;Shen, Zhanlong
As the most widespread mRNAs modification, N6‐methyladenosine (m6A) 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 m6A modification. Further experiments indicated that ALKBH5 may inhibit stability of PHF20 mRNA by removing the m6A modification of PHF20 mRNA 3′UTR. ALKBH5 suppresses CRC progression by decreasing PHF20 mRNA methylation. ALKBH5‐mediated m6A modification of PHF20 mRNA can serve as a hopeful strategy for the intervention and treatment of CRC. ALKBH5 expression is down‐regulated in CRC and plays a crucial tumor suppressive role. ALKBH5 inhibits the stability of PHF20 mRNA by removing the m6A modification. Targeting the ALKBH5‐mediated m6A modification of PHF20 mRNA may be a promising therapeutic strategy for intervention and treatment of CRC.
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影响因子：
4.1
作者：
TUCK, MT
通讯作者：
TUCK, MT
DOI：
10.1002/gcc.22924
发表时间：
2021-04
期刊：
Genes, chromosomes & cancer
影响因子：
--
作者：
Sugai T;Osakabe M;Sugimoto R;Eizuka M;Tanaka Y;Yanagawa N;Otsuka K;Sasaki A;Matsumoto T;Suzuki H
通讯作者：
Suzuki H
影响因子：
2.8
作者：
Yang, Peipei;Wang, Qian;Feng, Jinzhou
通讯作者：
Feng, Jinzhou
影响因子：
4.4
作者：
Wang, Y;Han, KJ;Chen, WF
通讯作者：
Chen, WF
人RNAN⁶-甲基杜氏丁基脱甲基酶AlkBH5的结构提供了有关其核酸识别和脱甲基化机制的见解。
影响因子：
14.9
作者：
Aik W;Scotti JS;Choi H;Gong L;Demetriades M;Schofield CJ;McDonough MA
通讯作者：
McDonough MA