N6 -methyladenosine (m6 A) RNA modification of G protein-coupled receptor 133 increases proliferation of lung adenocarcinoma.

Lung adenocarcinoma (LUAD) accounts for almost 40% of lung cancers, leading to significant associated morbidity and mortality rates. However, the mechanism of LUAD tumorigenesis remains far from clear. Here, we scanned down-regulated genes involved in LUAD sourced from The Cancer Genome Atlas and Gene Expression Omnibus data and focused on G protein-coupled receptor 133 (GPR133). We offer compelling evidence that GPR133 was expressed at low levels in the setting of LUAD, and higher expression was positively related to a better prognosis among patients with LUAD. Functionally, GPR133 inhibited cell proliferation and tumor growth in vitro and in vivo. Regarding the mechanism, flow cytometry assays and western blot assays showed that GPR133 enhanced p21 and decreased cyclin B1 expression, thus triggering LUAD cells at G2/M-phase arrest. Consistent with this, we evaluated the expression levels of cell-cycle biomarkers and found that bioinformatics analysis combined with N6 -methyladenosine (methylation at the N6 position in adenosine) RNA immunoprecipitation-qPCR assay indicated that GPR133 expression was down-regulated by this modification. Moreover, we observed that methyltransferase-like 3 was impaired in LUAD, and that it is able to significantly increase levels of GPR133 by enhancing its RNA stability. In conclusion, we found that GPR133 expression was down-regulated in LUAD via N6 -methyladenosine modification. Increasing GPR133 levels could suppress LUAD cell proliferation and tumor growth. © 2021 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Citation

Guixiong Wu, Dongfeng Zhai, Jiemei Xie, Shuiquan Zhu, Zhuo Liang, Xin Liu, Ziwen Zhao. N6 -methyladenosine (m6 A) RNA modification of G protein-coupled receptor 133 increases proliferation of lung adenocarcinoma. FEBS open bio. 2022 Mar;12(3):571-581

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PMID: 34185971

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