Loss of NEIL3 activates radiotherapy resistance in the progression of prostate cancer
| Autor: | Zean Li, Xu Chen, Hui Li, Qianghua Zhou, Wenli Cai, Zhongqiu Xie, Shirong Peng, Kaiwen Li, Hai Huang, Jin Yang, Fujun Qin, Qiong Wang, Kai Yao |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Male
Cancer Research medicine.medical_treatment Cell urologic and male genital diseases Flow cytometry Prostate cancer RNA interference Cell Line Tumor medicine Animals Humans Gene knockdown medicine.diagnostic_test business.industry Transfection Cell cycle medicine.disease Carcinoma Neuroendocrine Gene Expression Regulation Neoplastic Radiation therapy Prostatic Neoplasms Castration-Resistant medicine.anatomical_structure Oncology Cancer research RNA RNA Interference business |
| Zdroj: | Cancer Biology & Medicine. 19:1193-1210 |
| ISSN: | 2095-3941 |
| Popis: | Objective To explore the genetic changes in the progression of castration-resistant prostate cancer (CRPC) and neuroendocrine prostate cancer (NEPC) and the reason why these cancers resist existing therapies. Methods We employed our CRPC cell line microarray and other CRPC or NEPC datasets to screen the target gene NEIL3. Lentiviral transfection and RNA interference were used to construct overexpression and knockdown cell lines. Cell and animal models of radiotherapy were established by using a medical electron linear accelerator. Flow cytometry was used to detect apoptosis or cell cycle progression. Western blot and qPCR were used to detect changes in the protein and RNA levels. Results TCGA and clinical patient datasets indicated that NEIL3 was downregulated in CRPC and NEPC cell lines, and NEIL3 was correlated with a high Gleason score but a good prognosis. Further functional studies demonstrated that NEIL3 had no effect on the proliferation and migration of PCa cells. However, cell and animal radiotherapy models revealed that NEIL3 could facilitate the radiotherapy sensitivity of PCa cells, while loss of NEIL3 activated radiotherapy resistance. Mechanistically, we found that NEIL3 negatively regulated the expression of ATR, and higher NEIL3 expression repressed the ATR/CHK1 pathway, thus regulating the cell cycle. Conclusions We demonstrated that NEIL3 may serve as a diagnostic or therapeutic target for therapy-resistant patients. |
| Databáze: | OpenAIRE |
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