NEAT1 Confers Radioresistance to Hepatocellular Carcinoma Cells by Inducing Autophagy through GABARAP

• Published in: International journal of molecular sciences Vol. 23; no. 2; p. 711
• Main Authors: Sakaguchi, Hiromi, Tsuchiya, Hiroyuki, Kitagawa, Yutaka, Tanino, Tomohiko, Yoshida, Kenji, Uchida, Nobue, Shiota, Goshi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10-01-2022; MDPI
• Subjects: Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Autophagy; Autophagy - genetics; Cancer therapies; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - radiotherapy; Cell Line, Tumor; GABARAP; GABARAP protein; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Hepatocellular carcinoma; Humans; Liver cancer; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; long noncoding RNA; Medical prognosis; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; NEAT1; Plasmids; Prognosis; Protein expression; Proteins; Radiation therapy; Radiation Tolerance - genetics; Radioresistance; Radiosensitivity; Ray generators; RNA Interference; RNA, Long Noncoding - genetics; Stem cells; Transcription; Transfection; γ-Aminobutyric acid; long noncoding RNA; autophagy; NEAT1; GABARAP; hepatocellular carcinoma; radioresistance
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23020711

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.