LincRNA-p21 knockdown enhances radiosensitivity of hypoxic tumor cells by reducing autophagy through HIF-1/Akt/mTOR/P70S6K pathway

Abstract Hypoxic conditions are common in solid tumors and have a significant effect on tumor progression, therapeutic and prognosis. Long noncoding RNAs (lncRNAs) are longer than 200 nucleotides and cannot be translated into proteins, which play important roles in some diseases including cancer. Although previous analysis have showed that long intergenic non-coding RNA (lincRNA)-p21 is hypoxia-responsive and functions as a new regulator of cell cycle, apoptosis and warburg effect in cervical cancer, its biological roles in hypoxic hepatoma and glioma are unknown. In this work, we found that X-ray irradiation or hypoxia treatment elevated lincRNA-p21 expression in SMMC7721 hepatoma and U251MG glioma cells. Knockdown of lincRNA-p21 induced G2/M phase arrest, promoted apoptosis, decreased cell proliferation and motility, and reduced autophagy through HIF-1/Akt/mTOR/P70S6K pathway in hypoxic tumor cells. Our results delineated a novel mechanism of lincRNA-p21 in enhancing hypoxic tumor cell radiosensitivity, which might provide valuable targets for radiation therapy for solid tumors, such as hepatoma and glioma.