miR-101 inhibits autophagy and enhances cisplatin-induced apoptosis in hepatocellular carcinoma cells

Abstract

Hepatocellular carcinoma (HCC) ranks third in cancer-related mortality due to late diagnosis and poor treatment options. Autophagy is a lysosome-mediated protein and organelle degradation process which is characterized by the formation of double-membrane vesicles, known as autophagosomes. Increasing evidence reveals that autophagy functions as a survival mechanism in liver cancer cells against drug-induced apoptosis. In this study, we found that autophagy was suppressed by miR-101 in the HCC cell line HepG2. miR-101 inhibited autophagy via targets including RAB5A, STMN1 and ATG4D. Moreover, miR-101 enhanced apoptosis induced by cisplatin in the HepG2 cell line. The possible mechanism of this effect may be through inhibition of autophagy. Our results indicate a novel and critical role for miR-101 and autophagy in the chemoresistance of cisplatin in HCC. We propose that gene therapy targeting miR-101/autophagy should be investigated further as a potential alternative therapeutic strategy for HCC.

Inhibition of microRNA-101 attenuates hypoxia/reoxygenation-induced apoptosis through induction of autophagy in H9c2 cardiomyocytes

“…Furthermore, they revealed that STMN1 overexpression partially rescued cells from miR-101-mediated inhibition of autophagy, and that inhibition of miR-101 sensitized breast cancer cells to drug-mediated cell death (10). Xu et al (16) reported similar results, indicating that miR-101 had an inhibitory effect on autophagy, and enhanced cisplatin-induced apoptosis in hepatocellular carcinoma HepG2 cells, potentially via the inhibition of autophagy by targeting RAB5A, STMN1 and ATG4D. In the present study, it was also revealed that RAB5A expression levels were significantly upregulated following inhibition of miR-101 in H9c2 cardiomyocytes.…”

“…In addition, it was confirmed that miR-101 directly targeted RAB5A via binding to the 3'-UTR of RAB5A mRNA in H9c2 cardiomyocytes. Their targeting association has also previously been revealed in breast cancer MCF7 cells and hepatocellular carcinoma HepG2 cells (10,16).…”

“…In the present study, it was demonstrated that H/R induced apoptosis in H9c2 cardiomyocytes, concurrently with the downregulation of miR-101. Further investigation identified a novel target of miR-101, RAB5A, which had previously been reported to be associated with autophagy (10,16,17). Subsequently, the role of miR-101 in the regulation of autophagy under H/R was further investigated and the results suggested that inhibition of miR-101 attenuated H/R-induced apoptosis, at least partially, via the induction of autophagy.…”

“…However, prolonged hypoxia and subsequent reperfusion may lead to excessive autophagy, which results in cardiomyocyte death by excessive self-digestion of organelles and proteins (10). Such abundant cardiomyocyte loss may result in contractile dysfunction and heart failure (16). The manipulation of autophagy may therefore become a promising therapeutic strategy for the prevention or treatment of numerous types of heart disease.…”

Autophagy impacts on oxaliplatin-induced hepatocarcinoma apoptosis via the IL-17/IL-17R-JAK2/STAT3 signaling pathway

“…Autophagy involves lysosomal-mediated degradation of cellular organelles and has been closely related to tumor -induced hepatocarcinoma apoptosis via the IL-17/IL-17R-JAK2/STAT3 signaling pathway JINGHUA WU 1,2 , JIAPEI GUO 2 , QING CAO 3 , YI WANG 2 , JUNMAO CHEN 2 , ZHIGANG WANG 4 and ZHIYONG YUAN occurrence and progression (18). A previous study reported that resistance to oxaliplatin in HepG2 cells could be recovered by inhibition of autophagy (19), which suggested opportunities for exploitation of autophagy as a therapeutic target in cancer.…”