Li Yao, Li Quan, Gu Jie, Qian Duocheng, Qin Xiaojing, Li Dujian
Department of Urology, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, China.
Department of Urology, Changzheng Hospital Affiliated to Naval Military Medical University, Shanghai, China.
Transl Cancer Res. 2020 Oct;9(10):5857-5867. doi: 10.21037/tcr-20-1858.
Prostate cancer (PCa) is the second leading cause of cancer-related deaths worldwide. Prostate-specific G-protein-coupled receptor (PSGR) has been identified as a new potential biomarker and therapeutic target for PCa. However, the influence of exosomal PSGR on PCa metastasis remains unknown. This study aimed to identify the regulatory role of exosomal PSGR in the bone microenvironment, prior to metastasis of PCa and the underlying mechanism.
hFOB1.19 cells were co-cultured with PC-3 exosomes exhibiting PSGR overexpression. Alkaline phosphatase (ALP) and von Kossa staining methods were used to measure the osteogenesis of hFOB1.19 cells. RNA sequencing was used to screen the downstream target genes of PSGR and the signaling pathways involved. The expression of the candidate genes was verified using quantitative real-time polymerase chain reaction (qRT-PCR).
ALP and von Kossa staining results showed that PC-3 exosomes with overexpressed PSGR enhanced osteogenesis of hFOB1.19 cells. A total of 853 mRNAs were differentially expressed in hFOB1.19 cells of the PSGR-overexpressing PC3 cell (PC3 exosome) group compared to the negative exosome control (NC) group, among which 182 mRNAs were significantly upregulated and 671 were downregulated. The functional enrichment and pathway analysis showed that differentially expressed mRNAs were mainly involved in cellular responses to interleukin-1 (IL1), chemotaxis, inflammation, transcriptional misregulation in cancer, and MAKP and NF-κB signaling pathways. qRT-PCR showed that levels of intercellular adhesion molecule-1 (ICAM1), RELB proto-oncogene, NF-κB subunit (RELB), and IL1 beta (IL1B) were significantly decreased in hFOB1.19 cells of the PSGR-overexpression group.
This study suggests that PSGR may regulate the MAKP and NF-κB signaling pathways involved in the process of bony metastases by targeting ICAM1, RELB, and IL1B.
前列腺癌（PCa）是全球癌症相关死亡的第二大主要原因。前列腺特异性G蛋白偶联受体（PSGR）已被确定为PCa的一种新的潜在生物标志物和治疗靶点。然而，外泌体PSGR对PCa转移的影响尚不清楚。本研究旨在确定外泌体PSGR在PCa转移之前在骨微环境中的调节作用及其潜在机制。
将hFOB1.19细胞与表现出PSGR过表达的PC-3外泌体共培养。采用碱性磷酸酶（ALP）和冯·科萨染色法检测hFOB1.19细胞的成骨作用。利用RNA测序筛选PSGR的下游靶基因及相关信号通路。使用定量实时聚合酶链反应（qRT-PCR）验证候选基因的表达。
ALP和冯·科萨染色结果显示，PSGR过表达的PC-3外泌体增强了hFOB1.19细胞的成骨作用。与阴性外泌体对照组（NC）相比，PSGR过表达的PC3细胞（PC3外泌体）组的hFOB1.19细胞中共有853个mRNA差异表达，其中182个mRNA显著上调，671个下调。功能富集和通路分析表明，差异表达的mRNA主要参与细胞对白介素-1（IL1）的反应、趋化作用、炎症、癌症中的转录失调以及丝裂原活化蛋白激酶（MAKP）和核因子κB（NF-κB）信号通路。qRT-PCR显示，PSGR过表达组的hFOB1.19细胞中细胞间黏附分子-1（ICAM1）、原癌基因RELB、NF-κB亚基（RELB）和白介素-1β（IL1B）的水平显著降低。
本研究表明，PSGR可能通过靶向ICAM1、RELB和IL1B来调节参与骨转移过程的MAKP和NF-κB信号通路。
