Histone demethylase KDM4C stimulates the proliferation of prostate cancer cells via activation of AKT and c-Myc

Ching Yu Lin, Bi Juan Wang, Bo Chih Chen, Jen Chih Tseng, Shih Sheng Jiang, Kelvin K. Tsai, Ying Ying Shen, Chiou Hwa Yuh, Zong Lin Sie, Wen Ching Wang, Hsing Jien Kung, Chih Pin Chuu

Research output: Contribution to journalArticle

Abstract

Our three-dimensional organotypic culture revealed that human histone demethylase (KDM) 4C, a histone lysine demethylase, hindered the acini morphogenesis of RWPE-1 prostate cells, suggesting its potential oncogenic role. Knockdown (KD) of KDM4C suppressed cell proliferation, soft agar colony formation, and androgen receptor (AR) transcriptional activity in PCa cells as well as reduced tumor growth of human PCa cells in zebrafish xenotransplantation assay. Micro-Western array (MWA) analysis indicated that KD of KDM4C protein decreased the phosphorylation of AKT, c-Myc, AR, mTOR, PDK1, phospho-PDK1 S241, KDM8, and proteins involved in cell cycle regulators, while it increased the expression of PTEN. Fluorescent microscopy revealed that KDM4C co-localized with AR and c-Myc in the nuclei of PCa cells. Overexpression of either AKT or c-Myc rescued the suppressive effect of KDM4C KD on PCa cell proliferation. Echoing the above findings, the mRNA and protein expression of KDM4C was higher in human prostate tumor tissues as compared to adjacent normal prostate tissues, and higher KDM4C protein expression in prostate tumors correlated to higher protein expression level of AKT and c-Myc. In conclusion, KDM4C promotes the proliferation of PCa cells via activation of c-Myc and AKT.

Original languageEnglish
Article number1785
JournalCancers
Volume11
Issue number11
DOIs
Publication statusPublished - Nov 2019

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Histone Demethylases
Prostatic Neoplasms
Prostate
Androgen Receptors
Cell Proliferation
Proteins
Neoplasms
Heterologous Transplantation
Zebrafish
Cell Nucleus
Morphogenesis
Agar
Microscopy
Cell Cycle
Phosphorylation
Messenger RNA
Growth

Keywords

  • AKT
  • C-Myc
  • KDM4C
  • Micro-western array
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Histone demethylase KDM4C stimulates the proliferation of prostate cancer cells via activation of AKT and c-Myc. / Lin, Ching Yu; Wang, Bi Juan; Chen, Bo Chih; Tseng, Jen Chih; Jiang, Shih Sheng; Tsai, Kelvin K.; Shen, Ying Ying; Yuh, Chiou Hwa; Sie, Zong Lin; Wang, Wen Ching; Kung, Hsing Jien; Chuu, Chih Pin.

In: Cancers, Vol. 11, No. 11, 1785, 11.2019.

Research output: Contribution to journalArticle

Lin, Ching Yu ; Wang, Bi Juan ; Chen, Bo Chih ; Tseng, Jen Chih ; Jiang, Shih Sheng ; Tsai, Kelvin K. ; Shen, Ying Ying ; Yuh, Chiou Hwa ; Sie, Zong Lin ; Wang, Wen Ching ; Kung, Hsing Jien ; Chuu, Chih Pin. / Histone demethylase KDM4C stimulates the proliferation of prostate cancer cells via activation of AKT and c-Myc. In: Cancers. 2019 ; Vol. 11, No. 11.
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abstract = "Our three-dimensional organotypic culture revealed that human histone demethylase (KDM) 4C, a histone lysine demethylase, hindered the acini morphogenesis of RWPE-1 prostate cells, suggesting its potential oncogenic role. Knockdown (KD) of KDM4C suppressed cell proliferation, soft agar colony formation, and androgen receptor (AR) transcriptional activity in PCa cells as well as reduced tumor growth of human PCa cells in zebrafish xenotransplantation assay. Micro-Western array (MWA) analysis indicated that KD of KDM4C protein decreased the phosphorylation of AKT, c-Myc, AR, mTOR, PDK1, phospho-PDK1 S241, KDM8, and proteins involved in cell cycle regulators, while it increased the expression of PTEN. Fluorescent microscopy revealed that KDM4C co-localized with AR and c-Myc in the nuclei of PCa cells. Overexpression of either AKT or c-Myc rescued the suppressive effect of KDM4C KD on PCa cell proliferation. Echoing the above findings, the mRNA and protein expression of KDM4C was higher in human prostate tumor tissues as compared to adjacent normal prostate tissues, and higher KDM4C protein expression in prostate tumors correlated to higher protein expression level of AKT and c-Myc. In conclusion, KDM4C promotes the proliferation of PCa cells via activation of c-Myc and AKT.",
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AU - Shen, Ying Ying

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AB - Our three-dimensional organotypic culture revealed that human histone demethylase (KDM) 4C, a histone lysine demethylase, hindered the acini morphogenesis of RWPE-1 prostate cells, suggesting its potential oncogenic role. Knockdown (KD) of KDM4C suppressed cell proliferation, soft agar colony formation, and androgen receptor (AR) transcriptional activity in PCa cells as well as reduced tumor growth of human PCa cells in zebrafish xenotransplantation assay. Micro-Western array (MWA) analysis indicated that KD of KDM4C protein decreased the phosphorylation of AKT, c-Myc, AR, mTOR, PDK1, phospho-PDK1 S241, KDM8, and proteins involved in cell cycle regulators, while it increased the expression of PTEN. Fluorescent microscopy revealed that KDM4C co-localized with AR and c-Myc in the nuclei of PCa cells. Overexpression of either AKT or c-Myc rescued the suppressive effect of KDM4C KD on PCa cell proliferation. Echoing the above findings, the mRNA and protein expression of KDM4C was higher in human prostate tumor tissues as compared to adjacent normal prostate tissues, and higher KDM4C protein expression in prostate tumors correlated to higher protein expression level of AKT and c-Myc. In conclusion, KDM4C promotes the proliferation of PCa cells via activation of c-Myc and AKT.

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