PLCε knockdown enhances the radiosensitivity of castration‑resistant prostate cancer via the AR/PARP1/DNA‑PKcs axis Corrigendum in /10.3892/or.2022.8433

Pu,Jun; Li,Ting; Liu,Nanjing; Luo,Chunli; Quan,Zhen; Li,Luo; Wu,Xiaohou

doi:10.3892/or.2020.7520

PLCε knockdown enhances the radiosensitivity of castration‑resistant prostate cancer via the AR/PARP1/DNA‑PKcs axis

Corrigendum in: /10.3892/or.2022.8433

Authors:
- Jun Pu
- Ting Li
- Nanjing Liu
- Chunli Luo
- Zhen Quan
- Luo Li
- Xiaohou Wu
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Affiliations: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Key Laboratory of Diagnostics Medicine Designated by The Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China
Published online on: February 26, 2020 https://doi.org/10.3892/or.2020.7520
Pages: 1397-1412
Copyright: © Pu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Radiotherapy (RT) has been used as a therapeutic option for treatment of prostate cancer (PCa) for a number of years; however, patients frequently develop RT resistance, particularly in castration‑resistant PCa (CRPC), although the underlying mechanisms remain unknown. Understanding the underlying mechanism of RT resistance in CRPC may potentially highlight novel targets to improve therapeutic options for patients with PCa. In the present study, the expression levels of phospholipase Cε (PLCε), androgen receptor (AR) and DNA‑dependent protein kinase catalytic subunit (PKcs) were examined in PCa tissue samples and PCa cells, and the effects of PLCε knockdown on AR and DNA damage repair (DDR)‑related molecules were determined. The association between PLCε, AR and Poly (ADP‑ribose) polymerase 1 (PARP1), as well as their respective roles in radiation resistance, were assessed using gene knockdown and pharmaceutical inhibitors or activators. A chromatin immunoprecipitation assay was used to determine the epigenetic regulatory effects of PLCε on PARP1. Animal experiments were performed to assess whether the mechanisms observed in vitro could be replicated in vivo. The expression levels of PLCε, AR and DNA‑PKcs were significantly upregulated in PCa, particularly in CRPC. PLCε knockdown reduced the viability and increased apoptosis of cells subjected to radiation. Additionally, PLCε deficiency suppressed DDR progression by downregulating an AR and PARP1 positive feedback loop and the associated downstream molecules following radiation. PLCε depletion also increased the presence of histone H3 lysine 27 trimethylation in the PARP1 promoter region, suggesting increased methylation of the PARP1 gene and thus resulting in reduced expression of PARP1. In vivo, PLCε knockdown significantly potentiated the effects of radiation on tumor growth. Taken together, the results of the present study demonstrated that PLCε knockdown enhanced the radiosensitivity of CRPC by downregulating the AR/PARP1/DNA‑PKcs axis.

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