miR-6071 inhibits hepatocellular carcinoma progression via targeting PTPN11

by Selleckchem | Dec 17 2023

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.

Comments:

The study you described provides important insights into the regulation of liver cancer stem cells (LCSCs) and their role in hepatocellular carcinoma (HCC) progression. Here's a summary of the key findings and implications of the study:

1. **Decreased miR-6071 Expression in LCSCs:** The study observed reduced expression of miR-6071 in liver cancer stem cells (LCSCs).

2. **miR-6071 Overexpression Inhibits LCSCs and HCC Cells:** Through gain-of-function assays, it was demonstrated that miR-6071 overexpression suppressed LCSCs' self-renewal and tumorigenesis. Additionally, miR-6071 overexpression inhibited the proliferation and migration of HCC cells.

3. **miR-6071 Targets PTPN11 mRNA:** Bioinformatics analysis and luciferase reporter assays identified PTPN11 mRNA as a target of miR-6071. PTPN11 interference and specific inhibitors reversed the effects of miR-6071 overexpression, suggesting that PTPN11 is involved in the regulation of LCSCs by miR-6071.

4. **Clinical Implications:** The study correlated miR-6071 expression levels with PTPN11 levels in HCC tissue samples. Patients with high miR-6071 expression derived more survival benefits from postoperative lenvatinib treatment, indicating that miR-6071 could serve as a biomarker for predicting the efficacy of lenvatinib treatment in HCC patients.

5. **Sensitization to Lenvatinib Treatment:** Upregulation of miR-6071 sensitized HCC cells to lenvatinib treatment, suggesting a potential therapeutic strategy for improving the efficacy of lenvatinib in HCC patients.

In summary, this study identifies miR-6071 as a key regulator of LCSCs and HCC progression. By targeting PTPN11 and sensitizing HCC cells to lenvatinib treatment, miR-6071 holds promise as a therapeutic target and a predictive biomarker for postoperative lenvatinib treatment in HCC patients. These findings contribute valuable information to the understanding of HCC biology and may have important implications for the development of targeted therapies in the future.