Background/Objectives: Regucalcin (RGN) is a calcium-binding protein and an oestrogen target gene, which has been shown to play essential roles beyond calcium homeostasis. Decreased RGN expression was identified in several cancers, including prostate cancer (PCa). However, it is unknown if the loss of RGN is a cause or a consequence of malignancy. Also, it needs confirmation if RGN oestrogenic regulation occurs through the G-protein-coupled oestrogen receptor (GPER). This study investigates howRGNknockdown affects prostate cell fate and metabolism and highlights the GPER/RGN interplay in PCa. Methods: Bioinformatic analysis assessed the relationship betweenRGNexpression levels and patients’ outcomes.RGNknockdown (siRNA) was performed in non-neoplastic prostate and castration-resistant PCa. Wild-type andRGNknockdown PCa cells were treated with the GPER agonist G1. Viability (MTT), proliferation (Ki-67 immunocytochemistry), apoptosis (caspase-3-like activity) and migration (Transwell assays) were evaluated. Spectrophotometric analysis was used to determine glucose consumption, lactate production and lactate dehydrogenase activity. Lipid content was assessed using the Oil Red assay. Results/conclusions: Bioinformatic analysis showed that the loss ofRGNcorrelates with the development of metastatic PCa and poor survival outcomes.RGNknockdown induced a cancer-like phenotype in PNT1A cells, indicated by increased cell viability and proliferation and reduced apoptosis. In DU145 PCa cells,RGNknockdown augmented migration and enhanced the glycolytic profile, which indicates increased aggressiveness, in line with patients’ data. GPER activation modulated RGN expression in PCa cells andRGNknockdown in DU145 cells influenced GPER actions, which highlighted an interplay between these molecular players with relevance for their potential use as biomarkers or therapeutic targets.
背景/目的：Regucalcin（RGN）是一种钙结合蛋白，也是雌激素靶基因，已被证明在钙稳态之外发挥重要作用。包括前列腺癌（PCa）在内的多种癌症中均发现RGN表达降低。然而，尚不清楚RGN的缺失是恶性肿瘤的原因还是结果。此外，RGN的雌激素调节是否通过G蛋白偶联雌激素受体（GPER）发生也需要证实。本研究探讨了RGN敲低如何影响前列腺细胞的命运和代谢，并强调了GPER/RGN在前列腺癌中的相互作用。方法：通过生物信息学分析评估RGN表达水平与患者预后之间的关系。在非肿瘤性前列腺和去势抵抗性前列腺癌中进行RGN敲低（siRNA）。用GPER激动剂G1处理野生型和RGN敲低的前列腺癌细胞。评估了细胞活力（MTT）、增殖（Ki-67免疫细胞化学）、凋亡（caspase-3样活性）和迁移（Transwell实验）。使用分光光度法分析测定葡萄糖消耗、乳酸生成和乳酸脱氢酶活性。使用油红O染色法评估脂质含量。结果/结论：生物信息学分析表明，RGN的缺失与转移性前列腺癌的发展和不良生存结局相关。RGN敲低在PNT1A细胞中诱导了类似癌症的表型，表现为细胞活力和增殖增加以及凋亡减少。在DU145前列腺癌细胞中，RGN敲低增强了迁移并提高了糖酵解特征，这表明侵袭性增加，与患者数据一致。GPER激活调节前列腺癌细胞中RGN的表达，而DU145细胞中的RGN敲低影响了GPER的作用，这突出了这些分子参与者之间的相互作用，与其作为生物标志物或治疗靶点的潜在用途相关。
肿瘤(癌症)患者之家