The m6A methyltransferase METTL16 inhibits the proliferation of pancreatic adenocarcinoma cancer cells via the p21 signaling pathway

• DOI: 10.3389/fonc.2023.1138238
• Publication Date: 2023-04-25T05:05:17Z
• Authors: Fuming Xie; Yao Zheng; Wen Fu; Bojing Chi; Xianxing Wang; Junfeng Zhang; Jianyou Gu; Jingyang Yin; Qiang Zhou; Shixiang Guo; Lei Cai; Jiali Yang; Songsong Liu; Huaizhi Wang
• Keywords: 0301 basic medicine; 0303 health sciences; cell proliferation; p21; Oncology; pancreatic adenocarcinoma; METTL16; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; m6A; RC254-282

Background Many studies have reported that N6-methyladenosine (m6A) modification plays a critical role in the epigenetic regulation of organisms and especially pathogenesis malignant diseases. However, m6A research has mainly focused on methyltransferase activity mediated by METTL3, few METTL16. The aim this study was to investigate mechanism METTL16, which mediates modification, its pancreatic adenocarcinoma (PDAC) cell proliferation. Methods Clinicopathologic survival data were retrospectively collected from 175 PDAC patients multiple clinical centers detect expression CCK-8, cycle, EdU xenograft mouse model experiments used evaluate proliferation effect Potential downstream pathways mechanisms explored via RNA sequencing, bioinformatic analyses. Regulatory studied through inhibition, RIP, MeRIP‒qPCR assays. Results We found METTL16 markedly downregulated PDAC, multivariate Cox regression analyses revealed protective factor for patients. also demonstrated overexpression inhibited Furthermore, we identified METTL16-p21 signaling axis, with downregulation resulting inhibition CDKN1A (p21). Additionally, silencing highlighted alterations PDAC. Conclusions tumor-suppressive suppresses p21 pathway mediating modification. may be novel marker carcinogenesis target treatment