RRC ID 69980
Author Sakaguchi H, Tsuchiya H, Kitagawa Y, Tanino T, Yoshida K, Uchida N, Shiota G.
Title NEAT1 Confers Radioresistance to Hepatocellular Carcinoma Cells by Inducing Autophagy through GABARAP.
Journal Int J Mol Sci
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.
Volume 23(2)
Published 2022-1-10
DOI 10.3390/ijms23020711
PII ijms23020711
PMID 35054896
PMC PMC8775719
MeSH Apoptosis Regulatory Proteins / genetics* Apoptosis Regulatory Proteins / metabolism Autophagy / genetics* Carcinoma, Hepatocellular / genetics Carcinoma, Hepatocellular / metabolism Carcinoma, Hepatocellular / radiotherapy Cell Line, Tumor Gene Expression Regulation, Neoplastic* Gene Knockdown Techniques Humans Liver Neoplasms / genetics Liver Neoplasms / metabolism Liver Neoplasms / pathology Microtubule-Associated Proteins / genetics* Microtubule-Associated Proteins / metabolism Prognosis RNA Interference* RNA, Long Noncoding / genetics* Radiation Tolerance / genetics*
IF 4.556
Human and Animal Cells HuH-6(RCB1367)
DNA material mCherry-LC3B (RDB15159)