Downregulation of MUC15 by miR-183-5p.1 promotes liver tumor-initiating cells properties and tumorigenesis via regulating c-MET/PI3K/AKT/SOX2 axis.

ABSTRACT: Mucin 15 (MUC15) is reportedly aberrant in human malignancies, including hepatocellular carcinoma (HCC). However, the role of MUC15 in the regulation of liver tumor-initiating cells (T-ICs) remains unknown. Here, we report that expression of MUC15 is downregulated in liver T-ICs, chemoresistance and recurrent HCC samples. Functional studies reveal that MUC15 inhibits hepatoma cells self-renewal, malignant proliferation, tumorigenicity, and chemoresistance. Mechanistically, MUC15 interacts with c-MET and subsequently inactivates the PI3K/AKT/SOX2 signaling pathway. Moreover, we find that miR-183-5p.1 directly targets MUC15 3'-UTR in liver T-ICs. Coincidentally, SOX2 feedback inhibits MUC15 expression by directly transactivating miR-183-5p.1, thus completing a feedforward regulatory circuit

SUBMITTER: Han T 

PROVIDER: S-EPMC8891362 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature