m6A methylation mediates LHPP acetylation as a tumour aerobic glycolysis suppressor to improve the prognosis of gastric cancer

• DOI: 10.1038/s41419-022-04859-w
• Publication Date: 2022-05-14T12:09:45Z
• Authors: Jian-Xian Lin; Ning-Zi Lian; You-Xin Gao; Qiao-Ling Zheng; Ying-Hong Yang; Yu-Bin Ma; Zhi-Song Xiu; Qing-Zhu Qiu; Hua-Gen Wang; Chao-Hui Zheng; Ping Li; Jian-Wei Xie; Jun Lu; Qi-Yue Chen; Long-Long Cao; Mi Lin; Jia-Bin Wang; Chang-Ming Huang
• Keywords: 0301 basic medicine; QH573-671; Acetylation; Methylation; Article; 3. Good health; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Stomach Neoplasms; Cell Line, Tumor; Humans; RNA, Messenger; Cytology; Glycolysis; Cell Proliferation

Abstract LHPP, a histidine phosphatase, has been implicated in tumour progression. However, its role, underlying mechanisms, and prognostic significance human gastric cancer (GC) are elusive. Here, we obtained GC tissues corresponding normal from 48 patients identified LHPP as downregulated gene via RNA-seq. qRT-PCR western blotting were applied to examine levels tissues. The value of was elucidated using tissue microarray IHC analyses two independent cohorts. functional roles mechanistic insights growth metastasis evaluated vitro vivo. results showed that expression significantly decreased at both the mRNA protein levels. Multivariate Cox regression analysis revealed an factor effective predictor with GC. low related poor prognosis chemotherapy sensitivity patients. Moreover, elevated effectively suppressed Mechanistically, m6A modification by METTL14 represses expression; inhibits phosphorylation GSK3b through acetylation mediates HIF1A inhibit glycolysis, proliferation, invasion cells. Together, our findings suggest is regulated methylation regulates metabolism changing level. Thus, potential predictive biomarker therapeutic target for