Cancer Management and Research (May 2021)
Knockdown of Long Non-Coding RNA HCP5 Increases Radiosensitivity Through Cellular Senescence by Regulating microRNA-128 in Gliomas
Abstract
Cuihong Wang,1 Guanying Yu,2 Ying Xu,1 Chengfei Liu,1 Qian Sun,1 Wenqing Li,1 Junhua Sun,1 Yuhua Jiang,1 Lan Ye1 1Cancer Center, The Second Hospital of Shandong University, Jinan, Shandong, 250033, People’s Republic of China; 2Department of Gastrointestinal Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, 250013, People’s Republic of ChinaCorrespondence: Lan YeCancer Center, The Second Hospital of Shandong University, Jinan, Shandong, 250033, People’s Republic of ChinaEmail [email protected]: Glioma is the most common malignant brain tumor in adults. Radiation is a key therapy in glioma. However, the radioresistance of glioma was a big challenge. HLA complex P5 (HCP5) has been reported dysregulated in several types of malignant tumor, including glioma. The role of HCP5 in the radiosensitivity of glioma is so far unknown. The present study aimed to investigate the effect of HCP5 on radiosensitivity in gliomas.Methods: The levels of HCP5 and microRNA (miR)-128 were detected using qRT-PCR. The cell growth curve was used to show the cell proliferation and evaluate the radiosensitivity of glioma cells following exposure to X-ray. Senescence-associated β-galactosidase (SA-β-Gal) staining was used to test the cellular senescence. Luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to determine the correlation between HCP5 and miR-128.Results: HCP5 level of glioma cells was significantly higher than human astrocytes, whereas miR-128 level was lower in glioma cells. Besides, the HCP5 expression was increased in glioma tissues compared to normal brain tissues (NBTs). Knockdown of HCP5 inhibited cell proliferation and increased radiosensitivity in glioma cells. MiR-128 was predicted to be a target of HCP5. It was demonstrated that HCP5 directly bound to miR-128 and regulated its expression in glioma cells. Furthermore, the effects of HCP5 knockdown on radiosensitivity of glioma cells were attenuated by the inhibitor of miR-128.Conclusion: These findings suggested that interaction between lncRNA HCP5 and microRNA-128 could regulate the radiosensitivity of glioma cells by intervening in cellular senescence. This might be used as the potential radio-sensitization targets for glioma therapy.Keywords: glioma, radiosensitivity, HLA complex P5, microRNA-128, cellular senescence
