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ARNT‐dependent CCR8 reprogrammed LDH isoform expression correlates with poor clinical outcomes of prostate cancer
Author(s) -
Chen Guo,
Cai Zhiduan,
Lin Zhuoyuan,
Wang Cong,
Liang Yuxiang,
Han Zhaodong,
He Huichan,
Mo Rujun,
Lu Jianming,
Pan Bin,
Wu Chinlee,
Wang Fen,
Zhong Weide
Publication year - 2020
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.23201
Subject(s) - lactate dehydrogenase a , biology , prostate cancer , lactate dehydrogenase , cancer research , microbiology and biotechnology , cancer , gene isoform , biochemistry , gene , genetics , enzyme
Lactate dehydrogenase isozyme (LDH) is a tetramer constituted of two isoforms, LDHA and LDHB, the expression of which is associated with cell metabolism and cancer progression. Our previous study reveals that CC‐chemokine ligand‐18 (CCL18) is involved in progression of prostate cancer (PCa).This study aims to investigate how CCL18 regulates LDH isoform expression, and therefore, contributes to PCa progression. The data revealed that the expression of LDHA was upregulated and LDHB was downregulated in PCa cells by CCL18 at both messenger RNA and protein levels. The depletion of CCR8 reduced the ability of CCL18 to promote the proliferation, migration, and lactate production of PCa cells. Depletion of a CCR8 regulated transcription factor, ARNT, significantly reduced the expression of LDHA. In addition, The Cancer Genome Atlas dataset analyses revealed a positive correlation between CCR8 and ARNT expression. Two dimension difference gel electrophoresis revealed that the LDHA/LDHB ratio was increased in the prostatic fluid of patients with PCa and PCa tissues. Furthermore, increased LDHA/LDHB ratio was associated with poor clinical outcomes of patients with PCa. Together, our results indicate that the CCR8 pathway programs LDH isoform expression in an ARNT dependent manner and that the ratio of LDHA/LDHB has the potential to serve as biomarkers for PCa diagnosis and prognosis.