miR-6071 inhibits hepatocellular carcinoma progression via targeting PTPN11.

Abstract

Hepatocellular carcinoma (HCC) is a deadly malignancy. Liver cancer stem cells (LCSCs) participated in HCC progression and caused failure of chemotherapy. However, the underlying mechanism for the LCSCs regulation was unclear. In this study, we found that miR-6071 expression was decreased in LCSCs. Gain-of-function assays showed that miR-6071 overexpression repressed LCSCs self-renewal and tumorigenesis and inhibited HCC cells proliferation and migration. In mechanism, bioinformatics and luciferase reporter assay demonstrated that miR-6071 targeted 3'UTR of PTPN11 mRNA. Pearson analysis revealed a negative correlation between miR-6071 expression and PTPN11 levels in HCC tissue samples. Further study showed that PTPN11 interference and specific inhibitors IACS-13909 abrogated the discrepancy of self-renewal ability, proliferation, migration and tumorigenicity capacity between miR-6071 overexpression HCC cells and control cells. Moreover, upregulation of miR-6071 sensitized HCC cells to lenvatinib treatment. Clinical cohort analysis revealed that HCC patients with high miR-6071 expression got more survival benefit from postoperative lenvatinib treatment than patients with low miR-6071 levels. In conclusion, our study demonstrated a regulation mechanism of LCSCs, a target against LSCSs, and a biomarker for postoperative lenvatinib treatment.

• Authors: Minyong Chen, Huaxiang Wang, Songchang Shi, Hui Zhang, Shaohua Xu, Yi Jiang
• Journal: Archives of biochemistry and biophysics (Arch Biochem Biophys) Vol. 727 Pg. 109345 (09 30 2022) ISSN: 1096-0384 [Electronic] United States
• PMID: 35792156 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022. Published by Elsevier Inc.

Chemical References

• 3' Untranslated Regions
• MicroRNAs
• PTPN11 protein, human
• Protein Tyrosine Phosphatase, Non-Receptor Type 11

Topics

• 3' Untranslated Regions
• Carcinoma, Hepatocellular (pathology)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Gene Expression Regulation, Neoplastic
• Humans
• Liver Neoplasms (pathology)
• MicroRNAs (genetics, metabolism)
• Protein Tyrosine Phosphatase, Non-Receptor Type 11 (genetics, metabolism)