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

Abstract

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.

Non-coding RNA in cancer

“…while suppression of miR-126 triggered apoptosis and inhibited B-ALL progression in xenograft mice. miR-155 has been identified as an oncogene in many kinds of cancers, including colon, breast, lung, gastric and liver cancer [10][11][12][13][14]. In agreement with its oncogenic roles, miR-155 has been regarded as a therapeutic target in different cancers.…”

ATG5: A central autophagy regulator implicated in various human diseases

“…The impact of miR‐155‐5p on autophagy and apoptosis in HepG2/ADR cells was partly reversed by ATG5 . miR‐155‐5p was shown to overcome ADR resistance in liver cancer by targeting ATG5, which may be used as a target for liver cancer therapy 208 . Antifibrosis activity of quercetin attenuated rabbit tracheal stenosis via the TGF‐β/AKT/mTOR signaling pathway.…”

A narrative review of research progress on FoxM1 in breast cancer carcinogenesis and therapeutics

“…Speaking of miRNAs, it has been proved that miRNAs are a type of endogenous, small, single-stranded ncRNAs with a length of about 18-24 bases, which regulate the expression of genes at the post-transcriptional level (92,93). Numerous studies have indicated that miRNAs play predominant roles in the process of tumor cell proliferation, invasion, metastasis, relapse, and drug resistance (2,94,95).…”