p62 promotes proliferation, apoptosis‑resistance and invasion of prostate cancer cells through the Keap1/Nrf2/ARE axis

Jiang,Ganggang; Liang,Xue; Huang,Yiqiao; Lan,Ziquan; Zhang,Zhiming; Su,Zhengming; Fang,Zhiyuan; Lai,Yuxiong; Yao,Wenxia; Liu,Ting; Hu,La; Wang,Fen; Huang,Hai; Liu,Leyuan; Jiang,Xianhan

doi:10.3892/or.2020.7527

p62 promotes proliferation, apoptosis‑resistance and invasion of prostate cancer cells through the Keap1/Nrf2/ARE axis

Authors:
- Ganggang Jiang
- Xue Liang
- Yiqiao Huang
- Ziquan Lan
- Zhiming Zhang
- Zhengming Su
- Zhiyuan Fang
- Yuxiong Lai
- Wenxia Yao
- Ting Liu
- La Hu
- Fen Wang
- Hai Huang
- Leyuan Liu
- Xianhan Jiang
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Affiliations: Department of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510700, P.R. China, Department of Center Laboratory, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510700, P.R. China, Center for Translational Cancer Research, Texas A&M Institute of Biosciences and Technology, Texas A&M University, Houston, TX 77030, USA, Department of Urology, The Sun Yat‑sen Memorial Hospital, Sun Yat‑sen University, Guangzhou 510120, P.R. China
Published online on: February 28, 2020 https://doi.org/10.3892/or.2020.7527
Pages: 1547-1557
Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Prostate cancer poses a public health threat to hundreds of people around the world. p62 has been identified as a tumor suppressor, however, the mechanism by which p62 promotes prostate cancer remains poorly understood. The present study aimed to investigate whether p62 promotes proliferation, apoptosis resistance and invasion of prostate cancer cells via the Kelch‑like ECH‑associated protein 1/nuclear factor erytheroid‑derived 2‑like 2/antioxidant response element (Keap1/Nrf2/ARE) axis. Immunohistochemical staining and immunoblotting were performed to determine the protein levels. Rates of proliferation, invasion and apoptosis of prostate cancer cells were assessed using an RTCA system and flow cytometric assays. Levels of reactive oxygen species (ROS) were assessed using Cell ROX Orange reagent and mRNA levels of Nrf2 target genes were detected by qRT‑PCR. It was revealed that p62 increased the levels and activities of Nrf2 by suppressing Keap1‑mediated proteasomal degradation in prostate cancer cells and tissues, and high levels of p62 promoted growth of prostate cancer through the Keap1/Nrf2/ARE system. Silencing of Nrf2 in DU145 cells overexpressing p62 led to decreases in the rate of cell proliferation and invasion and an increase in the rate of cell apoptosis. p62 activated the Nrf2 pathway, promoted the transcription of Nrf2‑mediated target genes and suppressed ROS in prostate cancer. Therefore, p62 promoted the development of prostate cancer by activating the Keap1/Nrf2/ARE pathway and decreasing p62 may provide a new strategy to ameliorate tumor aggressiveness and suppress tumorigenesis to improve clinical outcomes.

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