Department of Urology, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai 20081, China; Department of Urology, Changzheng Hospital Affiliated to Naval Military Medical University, Shanghai 200003, China.
Department of Urology, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai 20081, China.
Life Sci. 2021 Jan 1;264:118638. doi: 10.1016/j.lfs.2020.118638. Epub 2020 Oct 24.
Prostate-specific G-protein coupled receptor (PSGR) in prostate cancer (Pca) are associated with poor overall survival. However, the effect of exosomal PSGR on PCa metastasis remains unknown.
The effect of exosome derived from PSGR-overexpressed PC3 cells (PC3 exosomes) on migration, invasion, epithelial-mesenchymal transition (EMT) and stemness of low invasive cells (LNCaP and RWPE-1) was assessed. Transcriptome sequencing was performed to identify differentially expressed (DE) mRNAs in low invasive cells incubated by PC3 exosomes or negative control (NC) exosomes.
The PSGR was stably overexpressed in PC3 cells. The PC3 exosomes were internalized in LNCaP and RWPE-1cells, and significantly promoted cells migration and invasion. The expression of E-cadherin was decreased, and Vimentin, Snail, SOX2 and OCT4a was increased in low invasive cells after PC3 exosome incubation. Additionally, a total of 993 and 1170 DE mRNAs were respectively identified in LNCaP and RWPE-1 cells after PC3 exosome incubation, and 5 upregulated mRNAs and 11 down regulated mRNAs were shared. The DE mRNAs were predominantly implicated in "activation of Rho GTPase activity" and "response to zinc ion" in LNCaP cells, and "extracellular matrix organization" and "patterning of blood vessels" in RWPE-1 cells. The KEGG analysis showed the DE mRNAs were enriched in pathways associated with EMT such as "Adherens junction", "Cell adhesion molecules (CAMs)" and "Focal adhesion".
Exosomal PSGR promoted migration, invasion, stemness and epithelial-mesenchymal transitions, and reshaped the mRNAs profiling of LNCaP and RWPE-1 cells.
前列腺特异性 G 蛋白偶联受体（PSGR）在前列腺癌（Pca）中与总体生存不良相关。然而，外泌体 PSGR 对 PCa 转移的影响尚不清楚。
评估来自 PSGR 过表达 PC3 细胞（PC3 外泌体）的外泌体对低侵袭性细胞（LNCaP 和 RWPE-1）迁移、侵袭、上皮-间充质转化（EMT）和干性的影响。进行转录组测序以鉴定在低侵袭性细胞孵育 PC3 外泌体或阴性对照（NC）外泌体后差异表达（DE）的 mRNAs。
PSGR 在 PC3 细胞中稳定过表达。PC3 外泌体被 LNCaP 和 RWPE-1 细胞内化，并显著促进细胞迁移和侵袭。在低侵袭性细胞孵育 PC3 外泌体后，E-钙粘蛋白的表达降低，Vimentin、Snail、SOX2 和 OCT4a 的表达增加。此外，在 LNCaP 和 RWPE-1 细胞孵育 PC3 外泌体后，分别鉴定出 993 个和 1170 个 DE mRNAs，其中有 5 个上调的 mRNAs 和 11 个下调的 mRNAs是共享的。DE mRNAs 主要参与 LNCaP 细胞中的“Rho GTPase 活性激活”和“锌离子反应”，以及 RWPE-1 细胞中的“细胞外基质组织”和“血管模式”。KEGG 分析表明，DE mRNAs 富集在 EMT 相关途径中，如“粘着连接”、“细胞黏附分子（CAMs）”和“焦点黏附”。
外泌体 PSGR 促进了 LNCaP 和 RWPE-1 细胞的迁移、侵袭、干性和上皮-间充质转化，并重塑了它们的 mRNAs 图谱。
