Knockdown of lncRNA TUG1 Enhances Radiosensitivity of Prostate Cancer via the TUG1/miR-139-5p/SMC1A Axis

Dianhui Xiu,1 Lin Liu,1 Min Cheng,1 Xiaosong Sun,2 Xibo Ma3 1Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun 130021, Jilin, People’s Republic of China; 2Department of Thyroid-Head and Neck Surgery, Jilin Cancer Hospital, Changchun 130021, Jilin, People’s Republic of China; 3Department of Otolaryngology, Jilin Provincial People’s Hospital, Changchun 130021, Jilin, People’s Republic of ChinaCorrespondence: Lin Liu; Min ChengDepartment of Radiology, China-Japan Union Hospital of Jilin University, No. 126, Sendai Street, Changchun City, Jilin Province, People’s Republic of ChinaEmail uyigtl@163.com; nrwpne@163.comBackground: Prostate cancer (PCa) is a common malignant tumor of the urinary system in males. LncRNA taurine-upregulated gene 1 (TUG1) has been verified to play a crucial role in progression and prognosis of PCa. However, the functional mechanism of TUG1 remains unclear with radiosensitivity of PCa.Methods: Quantitative real-time PCR (qRT-PCR) was conducted to measure the transcription levels of genes. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis were employed to assess cell proliferation and apoptosis, respectively. Moreover, colony formation assay was used to measure colony survival. Western blot was performed to detect the relative proteins expression. The interaction among variables was predicted by online tool starbase, and then confirmed using the dual luciferase reporter assay. A xenograft mouse model was constructed to investigate the effect of TUG1 on tumor growth in vivo.Results: The levels of lncRNA TUG1 and SMC1A were remarkably increased, while miR-139-5p was downregulated in PCa. Patients with high expression of TUG1 showed a lower survival rate and poor prognosis. Knockdown of TUG1 inhibited PCa cell proliferation and colony survival fraction, and promoted apoptosis. Downregulation of miR-139-5p reversed the effects of TUG1 deletion on proliferation, apoptosis and colony survival fraction in PCa cells treated with 4 Gy of X-ray radiation. Moreover, TUG1 sponged miR-139-5p to regulate SMC1A expression. SMC1A deletion blocked the effects of TUG1 on the progression of PCa cells treated with 4 Gy of X-ray radiation. The tumor volume and weight were illustriously reduced with radiation and TUG1 silencing in xenograft model.Conclusion: Knockdown of lncRNA TUG1 enhanced radiosensitivity in PCa via the TUG1/miR-139-5p/SMC1A axis. It may become a promising target for PCa treatment.Keywords: TUG1, miR-139-5p, SMC1A, prostate cancer, radiosensitivity