Confers Radioresistance to Hepatocellular Carcinoma Cells by Inducing Autophagy through GABARAP.

A long noncoding RNA (lncRNA), () (), is involved in the maintenance of cancer stem cells (CSCs) in hepatocellular carcinoma (HCC). CSCs are suggested to play important roles in therapeutic resistance. Therefore, we investigated whether is involved in the sensitivity to radiation therapy in HCC. Gene knockdown was performed using short hairpin RNAs, and -overexpressing HCC cell lines were generated by stable transfection with a -expressing plasmid DNA. Cells were irradiated using an X-ray generator. We found that knockdown enhanced the radiosensitivity of HCC cell lines and concomitantly inhibited autophagy. overexpression enhanced autophagy in the irradiated cells and conferred radioresistance. Gamma-aminobutyric acid receptor-associated protein (GABARAP) expression was downregulated by knockdown, whereas it was upregulated in -overexpressing cells. Moreover, GABARAP was required for -induced autophagy and radioresistance as its knockdown significantly inhibited autophagy and sensitized the cells to radiation. Since GABARAP is a crucial protein for the autophagosome-lysosome fusion, our results suggest that confers radioresistance to HCC by promoting autophagy through GABARAP.