Upregulated KDM4B promotes prostate cancer cell proliferation by activating autophagy. Issue 3 (29th August 2019)

• Record Type: Journal Article
• Authors: Sha, Jianjun; Han, Qing; Chi, Chenfei; Zhu, Yinjie; Pan, Jiahua; Dong, Baijun; Huang, Yiran; Xia, Weiliang; Xue, Wei
• Is Part Of: Journal of cellular physiology. Volume 235:Issue 3(2020:Mar.)
• Page Start: 2129
• Page End: 2138
• Publication Date: 2019-08-29
• Subjects: autophagy -- cell proliferation -- CRPC -- KDM4B -- prostate cancer; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.29117
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: Castration‐resistant prostate cancer (CRPC) causes most of the deaths in patients with prostate cancer (PCa). The androgen receptor (AR) axis plays an important role in castration resistance. Emerging studies showed that the lysine demethylase KDM4B is a key molecule in AR signaling and turnover, and autophagy plays an important role in CRPC. However, little is known about whether KDM4B promotes CRPC progression by regulating autophagy. Here we used an androgen‐independent LNCaP (LNCaP‐AI) cell line to assay aberrant KDM4B expression using qPCR and western blot analysis and investigated the function of KDM4B in regulating cell proliferation. We found that KDM4B was markedly increased in LNCaP‐AI cells compared with LNCaP cells. KDM4B level was significantly correlated with the Gleason score in PCa tissues. In vitro, KDM4B overexpression in CRPC cells promoted cell proliferation, whereas knockdown of KDM4B significantly inhibited cell proliferation. Upregulated KDM4B contributed to activate Wnt/β‐catenin signaling and autophagy. Moreover, KDM4B activated autophagy by regulating the Wnt/β‐catenin signaling. Finally, we demonstrated that autophagy inhibition attenuated KDM4B‐induced CRPC cell proliferation. Our results provided novel insights into the function of KDM4B‐driven CRPC development and indicated that KDM4B may be served as a potential target for CRPC therapy. Abstract : We used an androgen‐independent LNCaP (LNCaP‐AI) cell line to assay aberrant KDM4B expression using qPCR and western blot analysis and investigated the function of KDM4B on regulating cell proliferation. We found that KDM4B was markedly increased in LNCaP‐AI cells compared with LNCaP cells.