The KRAS/Lin28B axis maintains stemness of pancreatic cancer cells via the let-7i/TET3 pathway.

ABSTRACT: Increasing evidence demonstrates that Lin28B plays critical roles in numerous biological processes including cell proliferation and stemness maintenance. However, the molecular mechanisms underlying Lin28B nuclear translocation remain poorly understood. Here, we found for the first time that KRAS promoted Lin28B nuclear translocation through PKCβ, which directly bound to and phosphorylated Lin28B at S243. Firstly, we observed that Lin28B was upregulated in pancreatic cancer, contributing to cellular migration and proliferation. Furthermore, nuclear Lin28B upregulated TET3 messenger RNA and protein levels by blocking the production of mature let-7i. Subsequently, increased TET3 expression could also promote the expression of Lin28B, thereby forming a Lin28B/let-7i/TET3 feedback loop. Our re

SUBMITTER: Liu Y 

PROVIDER: S-EPMC7782082 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature