ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2023; 14(7):1117-1131. doi:10.7150/jca.84070 This issue Cite
Research Paper
METTL14 Facilitates the Metastasis of Pancreatic Carcinoma by Stabilizing LINC00941 in an m6A-IGF2BP2-Dependent Manner
Department of Gastroenterology, Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China.
†These authors contributed equally to this work and share first authorship.
Abstract
Pancreatic adenocarcinoma (PC), one of the most fatal diseases, usually generates a poor prognosis in advanced stages. N6-methyladenosine modification has emerged as a crucial participant in tumor development and recurrence. Methyltransferase-like 14 (METTL14), as a core member of methyltransferases, is involved in tumor progression and metastasis. However, the potential mechanism by which METTL14 regulates long noncoding RNAs (lncRNAs) in PC remains unclear. RNA immunoprecipitation (RIP), methylated RNA immunoprecipitation quantitative PCR (MeRIP-qPCR), and fluorescence in situ hybridization (FISH) were used to explore the underlying mechanisms. In our study, we found that METTL14 expression was upregulated in PC patients, and was associated with poor prognosis. In vitro and in vivo experiments, knocking down METTL14 suppressed tumor metastasis. RNA-seq and bioinformatics analyses were used to identify LINC00941 as the downstream target of METTL14. Mechanistically, LINC00941 was upregulated by METTL14 in an m6A-dependent way. LINC00941 was recruited and recognized by IGF2BP2. METTL14 enhanced the affinity of IGF2BP2 for LINC00941, while IGF2BP2 promoted the stabilization of LINC00941, which contributed to the migration and invasion of PC cells. Overall, our research revealed that METTL14 promoted the metastasis of PC through m6A modification of LINC00941. Targeting the METTL14-LINC00941-IGF2BP2 axis may provide promising therapeutic approaches for PC.
Keywords: pancreatic carcinoma, METTL14, metastasis, LINC00941, IGF2BP2, N6-methyladenosine
Citation styles
