miR-6071 inhibits hepatocellular carcinoma progression via targeting PTPN11

Minyong Chen; Huaxiang Wang; Songchang Shi; Hui Zhang; Shaohua Xu; Yi Jiang

doi:10.1016/j.abb.2022.109345

miR-6071 inhibits hepatocellular carcinoma progression via targeting PTPN11

Arch Biochem Biophys. 2022 Sep 30:727:109345. doi: 10.1016/j.abb.2022.109345. Epub 2022 Jul 2.

Authors

Minyong Chen¹, Huaxiang Wang², Songchang Shi³, Hui Zhang¹, Shaohua Xu¹, Yi Jiang⁴

Affiliations

¹ Department of Hepatobiliary and Pancreatic Surgery, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, 350014, Fuzhou, Fujian Province, China.
² Department of Hepatobiliary and Pancreatic Surgery, Fuzong Clinical Medical College of Fujian Medical University, 350025, Fuzhou, Fujian Province, China.
³ Department of Critical Care Medicine, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital South Brance, Fujian Provincial Hospital Jinshan Branch, 350001, Fuzhou, Fujian Province, China.
⁴ Department of Hepatobiliary and Pancreatic Surgery, Fuzong Clinical Medical College of Fujian Medical University, 350025, Fuzhou, Fujian Province, China. Electronic address: fjykdxcmy@sina.cn.

PMID: 35792156
DOI: 10.1016/j.abb.2022.109345

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.

Keywords: Hepatocellular carcinoma; Lenvatinib; Liver cancer stem cells; PTPN11; miR-6071.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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