RT Journal Article
SR Electronic
T1 Loss of NEIL3 activates radiotherapy resistance in the progression of prostate cancer
JF Cancer Biology & Medicine
JO Cancer Biology & Medicine
FD China Anti-Cancer Association
SP 20200550
DO 10.20892/j.issn.2095-3941.2020.0550
A1 Qiong Wang
A1 Zean Li
A1 Jin Yang
A1 Shirong Peng
A1 Qianghua Zhou
A1 Kai Yao
A1 Wenli Cai
A1 Zhongqiu Xie
A1 Fujun Qin
A1 Hui Li
A1 Xu Chen
A1 Kaiwen Li
A1 Hai Huang
YR 2021
UL http://www.cancerbiomed.org/content/early/2022/07/15/j.issn.2095-3941.2020.0550.abstract
AB 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.