Long noncoding RNA LINC00958 regulates cell sensitivity to radiotherapy through RRM2 by binding to microRNA‐5095 in cervical cancer

• Published in: Journal of cellular physiology 2019-12, Vol.234 (12), p.23349-23359
• Main Authors: Zhao, Hui, Zheng, Guang‐Hong, Li, Guang‐Cai, Xin, Li, Wang, Yong‐Sheng, Chen, Ying, Zheng, Xue‐Mei
• Format: Article
• Language: English
• Subjects: Apoptosis; Cancer; Cell growth; Cell proliferation; Cell survival; Cervical cancer; Cervix; Gene expression; Genomes; Gynecological diseases; Irradiation; long noncoding RNA LINC00958; MicroRNAs; microRNA‐5095; miRNA; Radiation dosage; Radiation therapy; Radiation tolerance; Reductase; Reductases; Ribonucleic acid; ribonucleotide reductase subunit M2; RNA; Sensitivity analysis; sensitivity to radiotherapy; Survival; Tumors; Xenografts; Xenotransplantation
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.28902

Long noncoding RNAs (lncRNAs) have been implicated in the regulation of resistance to radiotherapy in cervical cancer, which is a type of gynecological disease with high mortality in women around the world. Hence, our purpose is to delineate the involvement of LINC00958 in regulating cell sensitivity to radiotherapy in cervical cancer. LINC00958 expression in cervical cancer was assayed, followed by verification of the relationship among LINC00958, microRNA‐5095 (miR‐5095) and ribonucleotide reductase subunit M2 (RRM2). Hela cells were transduced with up‐/downregulation of miR‐5095 or RRM2, or LINC00958 silencing, respectively, and then treated with or without a 6 Gy dose of X‐ray irradiation. Then the cell proliferation, apoptosis, survival fraction rate, as well as sensitivity to radiotherapy, were assessed. Finally, xenograft tumor in nude mice was established by transplanting Hela cells transfected with sh‐LINC00958 and irradiated with 6 Gy of X‐ray. High expression of LINC00958 was revealed in The Cancer Genome Atlas and Gene Expression Profiling Interactive Analysis, as well as in radiation‐resistant patients, which was associated with lower sensitivity to radiotherapy in cervical cancer. Moreover, cervical cancer patients with higher LINC00958 expression exhibited a shorter overall survival according to Kaplan–Meier analysis. In addition, LINC00958 could regulate the expression of RRM2 by competing for miR‐5095. A combination of radiotherapy with LINC00958 silencing, RRM2 downregulation or miR‐5095 overexpression was found to inhibit cervical cancer cell proliferation and tumor growth, while promoting cell apoptosis both in vitro and in vivo. Collectively, our results suggest that LINC00958 could regulate RRM2 by competing to miR‐5095, which regulates cell sensitivity to radiotherapy in cervical cancer. Collectively, our results suggest that LINC00958 could regulate ribonucleotide reductase subunit M2 (RRM2) by competing to microRNA‐5095 (miR‐5095), which regulates cell sensitivity to radiotherapy in cervical cancer.