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.

中文翻译：

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依赖ARNT的CCR8重编程的LDH亚型表达与前列腺癌的不良临床结局相关。

乳酸脱氢酶同工酶（LDH）是由两个同工型，LDHA和LDHB组成的四聚体，其表达与细胞代谢和癌症进展有关。我们先前的研究表明CC趋化因子配体18（CCL18）与前列腺癌（PCa）的进展有关。本研究旨在研究CCL18如何调节LDH亚型表达，从而促进PCa的进展。数据显示在信使RNA和蛋白质水平上，CCL18在PCa细胞中LDHA的表达上调，而LDHB下调。CCR8的消耗降低了CCL18促进PCa细胞增殖，迁移和乳酸生成的能力。CCR8调节的转录因子ARNT的耗竭显着降低了LDHA的表达。此外，癌症基因组图谱数据集分析显示，CCR8和ARNT表达之间呈正相关。二维差异凝胶电泳显示，PCa和PCa组织患者前列腺液中的LDHA / LDHB比值增加。此外，LDHA / LDHB比值升高与PCa患者的临床预后差有关。在一起，我们的结果表明，CCR8通路以ARNT依赖的方式编程LDH亚型表达，并且LDHA / LDHB的比率具有作为PCa诊断和预后的生物标志物的潜力。LDHA / LDHB比值升高与PCa患者的临床预后差有关。在一起，我们的结果表明，CCR8通路以ARNT依赖的方式编程LDH亚型表达，并且LDHA / LDHB的比率具有作为PCa诊断和预后的生物标志物的潜力。LDHA / LDHB比值升高与PCa患者的临床预后差有关。在一起，我们的结果表明，CCR8通路以ARNT依赖的方式编程LDH亚型表达，并且LDHA / LDHB的比率具有作为PCa诊断和预后的生物标志物的潜力。