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Knockdown of Long Non-Coding RNA HCP5 Increases Radiosensitivity Through Cellular Senescence by Regulating
Cuihong Wang1, Guanying Yu2, Ying Xu1
1Cancer Center, The Second Hospital of Shandong University, Jinan, Shandong, 250033, People's Republic of China.
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.
Insights
This study reveals that high HLA complex P5 (HCP5) levels increase glioma radioresistance by suppressing microRNA-128. Reducing HCP5 enhances radiosensitivity, suggesting HCP5 and microRNA-128 as potential targets for glioma therapy.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cancer Research
Background:
- Glioma is the most common adult malignant brain tumor, with radioresistance posing a significant therapeutic challenge.
- HLA Complex P5 (HCP5) is dysregulated in various cancers, but its role in glioma radiosensitivity remains unexplored.
Purpose of the Study:
- To investigate the impact of HCP5 on the radiosensitivity of glioma cells.
- To elucidate the molecular mechanisms underlying HCP5's influence on glioma radioresistance.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to measure HCP5 and microRNA (miR)-128 levels.
- Cell proliferation assays and senescence-associated β-galactosidase (SA-β-Gal) staining to assess radiosensitivity and cellular senescence.
- Luciferase reporter and RNA immunoprecipitation (RIP) assays to confirm the interaction between HCP5 and miR-128.
Main Results:
- HCP5 expression was elevated in glioma tissues and cells, inversely correlated with miR-128 levels.
- Knockdown of HCP5 significantly reduced glioma cell proliferation and enhanced radiosensitivity.
- HCP5 directly targets and regulates miR-128, and its effect on radiosensitivity is mediated through this interaction.
Conclusions:
- The interaction between long non-coding RNA (lncRNA) HCP5 and miR-128 regulates glioma cell radiosensitivity, potentially by affecting cellular senescence.
- HCP5 and miR-128 represent promising therapeutic targets for overcoming radioresistance in glioma treatment.
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