Mettl3 Promotes Pancreatic Cancer Proliferation And Stemness By Increasing Stability Of Id2 Mrna In A M6a-dependent Manner
Document Type
Article
Publication Date
5-19-2023
Publication Title
Cancer Letters
Abstract
In eukaryotes, N6-methyladenosine (m6A) is the most prevalent epigenetic alteration. Methyltransferase-like 3 (METTL3) is a key player in the control of m6A, although its function in pancreatic cancer is incompletely understood. In this study, we examined the role that METTL3 plays in pancreatic cancer cell proliferation and stemness. We discovered that in pancreatic cancer cells, METTL3-mediated m6A alterations regulate ID2 as a downstream target. The stability of ID2 mRNA was decreased and m6A modification was effectively eliminated by METTL3 knockdown in pancreatic cancer cells. We also demonstrate that m6a-YTHDF2 is necessary for the METTL3-mediated stabilization of ID2 mRNA. Additionally, we show that ID2 controls the stemness molecules NANOG and SOX2 via the PI3K-AKT pathway to support pancreatic cancer growth and stemness maintenance. Our data suggest that METTL3 may post-transcriptionally upregulate ID2 expression in an m6A-YTHDF2-dependent manner to further promote the stabilization of ID2 mRNA, which may be a new target for pancreatic cancer treatment.
PubMed ID
37196908
Volume
565
Recommended Citation
Chen, Jiaoshun; Zhang, Haoxiang; Xiu, Chaoyang; Gao, Chenggang; Wu, Shihong; Bai, Jianwei; Shen, Qiang; and Yin, Tao, "Mettl3 Promotes Pancreatic Cancer Proliferation And Stemness By Increasing Stability Of Id2 Mrna In A M6a-dependent Manner" (2023). School of Medicine Faculty Publications. 947.
https://digitalscholar.lsuhsc.edu/som_facpubs/947