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

研究成果: 雜誌貢獻文章

摘要

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.

原文英語
文章編號1785
期刊Cancers
11
發行號11
DOIs
出版狀態已發佈 - 十一月 2019

指紋

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

引用此文

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.

於: Cancers, 卷 11, 編號 11, 1785, 11.2019.

研究成果: 雜誌貢獻文章

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. 於: Cancers. 2019 ; 卷 11, 編號 11.
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title = "Histone demethylase KDM4C stimulates the proliferation of prostate cancer cells via activation of AKT and c-Myc",
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.",
keywords = "AKT, C-Myc, KDM4C, Micro-western array, Prostate cancer",
author = "Lin, {Ching Yu} and Wang, {Bi Juan} and Chen, {Bo Chih} and Tseng, {Jen Chih} and Jiang, {Shih Sheng} and Tsai, {Kelvin K.} and Shen, {Ying Ying} and Yuh, {Chiou Hwa} and Sie, {Zong Lin} and Wang, {Wen Ching} and Kung, {Hsing Jien} and Chuu, {Chih Pin}",
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T1 - Histone demethylase KDM4C stimulates the proliferation of prostate cancer cells via activation of AKT and c-Myc

AU - Lin, Ching Yu

AU - Wang, Bi Juan

AU - Chen, Bo Chih

AU - Tseng, Jen Chih

AU - Jiang, Shih Sheng

AU - Tsai, Kelvin K.

AU - Shen, Ying Ying

AU - Yuh, Chiou Hwa

AU - Sie, Zong Lin

AU - Wang, Wen Ching

AU - Kung, Hsing Jien

AU - Chuu, Chih Pin

PY - 2019/11

Y1 - 2019/11

N2 - 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.

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.

KW - AKT

KW - C-Myc

KW - KDM4C

KW - Micro-western array

KW - Prostate cancer

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