Stücheli Simon, Araya Selene, Ercan Caner, Moser Seraina O, Gallon John, Jenö Paul, Piscuoglio Salvatore, Terracciano Luigi, Odermatt Alex
Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, 4056 Basel, Switzerland.
Institute of Medical Genetics and Pathology, University Hospital Basel, 4031 Basel, Switzerland.
Cancers (Basel). 2022 Jun 23;14(13):3074. doi: 10.3390/cancers14133074.
Prostate cancer (PCa), one of the most common malignancies in men, typically responds to initial treatment, but resistance to therapy often leads to metastases and death. The dehydrogenase/reductase 7 (DHRS7, SDR34C1) is an "orphan" enzyme without known physiological function. DHRS7 was previously found to be decreased in higher-stage PCa, and siRNA-mediated knockdown increased the aggressiveness of LNCaP cells. To further explore the role of DHRS7 in PCa, we analyzed the proteome of LNCaP cells following knockdown to assess potentially altered pathways. Although DHRS7 is able to inactivate 5α-dihydrotestosterone, knockdown did not affect androgen receptor (AR) target gene expression, and its effect on PCa cells seems to be androgen-independent. Importantly, proteome analyses revealed increased expression of epidermal growth factor receptor (EGFR), which was confirmed by RT-qPCR and Western blotting. Comparison of AR-positive LNCaP with AR-negative PC-3 and DU145 PCa cell lines revealed a negative correlation between DHRS7 and EGFR expression. Conversely, knockdown enhanced DHRS7 expression in these cells. Importantly, analysis of patient samples revealed a negative correlation between DHRS7 and EGFR expression, both at the mRNA and protein levels, and DHRS7 expression correlated positively with patient survival rates. These results suggest a protective role for DHRS7 in PCa.
前列腺癌（PCa）是男性最常见的恶性肿瘤之一，通常对初始治疗有反应，但治疗耐药往往会导致转移和死亡。脱氢酶/还原酶7（DHRS7，SDR34C1）是一种没有已知生理功能的“孤儿”酶。先前发现DHRS7在晚期PCa中表达降低，并且siRNA介导的敲低增加了LNCaP细胞的侵袭性。为了进一步探究DHRS7在PCa中的作用，我们分析了敲低后LNCaP细胞的蛋白质组，以评估潜在改变的信号通路。尽管DHRS7能够使5α-二氢睾酮失活，但敲低并不影响雄激素受体（AR）靶基因的表达，并且其对PCa细胞的作用似乎与雄激素无关。重要的是，蛋白质组分析显示表皮生长因子受体（EGFR）的表达增加，这通过RT-qPCR和蛋白质印迹得到证实。将AR阳性的LNCaP与AR阴性的PC-3和DU145 PCa细胞系进行比较，发现DHRS7与EGFR表达之间呈负相关。相反，敲低增强了这些细胞中DHRS7的表达。重要的是，对患者样本的分析显示，在mRNA和蛋白质水平上，DHRS7与EGFR表达之间均呈负相关，并且DHRS7表达与患者生存率呈正相关。这些结果表明DHRS7在PCa中具有保护作用。
