Abstract
A long noncoding RNA (lncRNA), nuclear enriched abundant transcript 1 (NEAT1) variant 1 (NEAT1v1), 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 NEAT1v1 is involved in the sensitivity to radiation therapy in HCC. Gene knockdown was performed using short hairpin RNAs, and NEAT1v1-overexpressing HCC cell lines were generated by stable transfection with a NEAT1v1-expressing plasmid DNA. Cells were irradiated using an X-ray generator. We found that NEAT1 knockdown enhanced the radiosensitivity of HCC cell lines and concomitantly inhibited autophagy. NEAT1v1 overexpression enhanced autophagy in the irradiated cells and conferred radioresistance. Gamma-aminobutyric acid receptor-associated protein (GABARAP) expression was downregulated by NEAT1 knockdown, whereas it was upregulated in NEAT1v1-overexpressing cells. Moreover, GABARAP was required for NEAT1v1-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 NEAT1v1 confers radioresistance to HCC by promoting autophagy through GABARAP.
Highlights
Primary liver cancer is a malignant tumor with a poor prognosis and the third leading cause of cancer death worldwide [1]
That NEAT1v1 induced the the expression of type at the transcription level in hepatocellular carcinoma (HCC). These results suggest expression of at the transcription level in. These results suggest that that NEAT1v1 contributes to the establishment of HCC resistance to radiotherapy
NEAT1v1 and NEAT1v2 have the same transcriptionstart startsite, site,but buttheir theirtranscription transcription terminates at different positions without splicing
Summary
Primary liver cancer is a malignant tumor with a poor prognosis and the third leading cause of cancer death worldwide [1]. The emergence of radioresistant tumor cells is still a major obstacle for the clinical application of radiotherapy as a treatment against HCC. CSCs are likely resistant to chemotherapy and cells radiation therapy and might involved tumor recur‐. The association between radiosensitivity of HCC and NEAT1v1 remains to be the knockout (KO) of NEAT1 increased the cell sensitivity to those drugs [10]. Strated that the radioresistance was mediated by autophagy via gamma-aminobutyric tyric acid A receptor type A‐associated protein (GABARAP) and that NEAT1v1 induced acid These results suggest expression of at the transcription level in cells. These results suggest that that NEAT1v1 contributes to the establishment of HCC resistance to radiotherapy.
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