miR-155-5p increases the sensitivity of liver cancer cells to adriamycin by regulating ATG5-mediated autophagy.

Liver cancer is the sixth most prevalent cancer worldwide and the third leading cause of cancer-related deaths. Adriamycin (ADR) resistance, which often leads to the progression of malignant tumors, is a major treatment obstacle for liver cancer. It has been confirmed that miR-155-5p could reverse drug resistance in human breast cancer. However, the biological function of miR-155-5p in ADR-resistant liver carcinoma (HepG2/ADR) cells remains unclear. miR-155-5p and ATG5 expression was determined by RT-qPCR and western blot. In addition, MTT, flow cytometry, immunofluorescence staining, and western blotting were performed to evaluate the proliferation, apoptosis, and autophagy of liver cancer cells. Finally, the effect of miR-155-5p on the expression of autophagy-related 5 (ATG5) was analyzed by luciferase activity assay, western blot, and RT-qPCR. Our results showed that miR-155-5p was downregulated in HepG2/ADR cells. Increasing the expression of miR-155-5p enhanced the sensitivity of liver carcinoma cells to ADR and promoted apoptosis through inhibition of autophagy in vitro. In addition, the binding site between miR-155-5p and ATG5 was identified, and miR-155-5p could directly regulate ATG5. Finally, ATG5 partially rescued the effect of miR-155-5p on autophagy and the apoptosis of HepG2/ADR cells. In conclusion, our findings showed that miR-155-5p could reverse ADR resistance in liver cancer by targeting ATG5, which may function as a potential target for liver cancer treatment.

miR-34a-5p suppresses the invasion and metastasis of liver cancer by targeting the transcription factor YY1 to mediate MYCT1 upregulation.

BACKGROUND: In recent years, microRNAs (miRNAs) are reported to act as molecular biomarkers for cancer diagnosis, treatment, and prognosis (including liver cancer) and to be involved in the development and progression of cancer and other physiological and pathological changes. However, the role of miR-34a-5p in liver cancer is still largely unknown. METHODS: In our study, the expression of miR-34a-5p in liver cancer tissues and HCC cell lines was detected by qRT-PCR. The CCK-8, scratch wound-healing motility and Transwell assays were used to evaluate the effect on cell proliferation, migration and invasion. The expression of YY1, E-cadherin, N-cadherin and vimentin was analysed by western blotting. The dual luciferase assay was performed to confirm whether YY1 is a target of miR-34a-5p. The combination of YY1 and MYCT1 was detected by chromatin immunoprecipitation (ChIP) assay. RESULTS: The results showed that miR-34a-5p was downregulated in liver cancer tissues and HCC cell lines. Overexpression of miR-34a-5p inhibited the proliferation, migration and invasion of liver cancer cells. YY1 was a direct target of miR-34a-5p, and the expression of YY1 could reverse the influence of miR-34a-5p on the proliferation, migration and invasion of liver cancer cells. YY1 inhibited MYCT1 expression by directly binding to its promoter region, and knockdown of MYCT1 reversed the influence of miR-34a-5p on the proliferation, migration and invasion of liver cancer cells. CONCLUSION: Our results suggest that miR-34a-5p could inhibit the invasion and metastasis of hepatoma cells by targeting YY1-mediated MYCT1 transcriptional repression.