Knockdown of Long Non-Coding RNA HCP5 Increases Radiosensitivity Through Cellular Senescence by Regulating microRNA-128 in Gliomas

Cuihong Wang; Guanying Yu; Ying Xu; Chengfei Liu; Qian Sun; Wenqing Li; Junhua Sun; Yuhua Jiang; Lan Ye

doi:10.2147/CMAR.S301333

Knockdown of Long Non-Coding RNA HCP5 Increases Radiosensitivity Through Cellular Senescence by Regulating microRNA-128 in Gliomas

Cancer Manag Res. 2021 May 7:13:3723-3737. doi: 10.2147/CMAR.S301333. eCollection 2021.

Authors

Cuihong Wang¹, Guanying Yu², Ying Xu¹, Chengfei Liu¹, Qian Sun¹, Wenqing Li¹, Junhua Sun¹, Yuhua Jiang¹, Lan Ye¹

Affiliations

¹ Cancer Center, The Second Hospital of Shandong University, Jinan, Shandong, 250033, People's Republic of China.
² Department of Gastrointestinal Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, 250013, People's Republic of China.

Abstract

Introduction: 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: HLA complex P5; cellular senescence; glioma; microRNA-128; radiosensitivity.

Grants and funding

This work was supported by the Shandong Province Key Research and Development Plan [grant numbers 2019GSF108117]; the Young Taishan Scholars Program, Shandong, China [grant number: tsqn201909178]; Shandong Province Nature Science Foundation [grant number: ZR2020MH208]; the National Nature Science Foundation of China [grant number: 81902920]; and the Major Science and Technology Project of Shandong Province [grant number: 2014ZZCX02104].