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2.
Cell Death Dis ; 14(8): 502, 2023 08 04.
Article in English | MEDLINE | ID: mdl-37542027

ABSTRACT

Tumor-derived exosomes and their contents promote cancer metastasis. Phosphoglycerate mutase 1 (PGAM1) is involved in various cancer-related processes. Nevertheless, the underlying mechanism of exosomal PGAM1 in prostate cancer (PCa) metastasis remains unclear. In this study, we performed in vitro and in vivo to determine the functions of exosomal PGAM1 in the angiogenesis of patients with metastatic PCa. We performed Glutathione-S-transferase pulldown, co-immunoprecipitation, western blotting and gelatin degradation assays to determine the pathway mediating the effect of exosomal PGAM1 in PCa. Our results revealed a significant increase in exosomal PGAM1 levels in the plasma of patients with metastatic PCa compared to patients with non-metastatic PCa. Furthermore, PGAM1 was a key factor initiating PCa cell metastasis by promoting invadopodia formation and could be conveyed by exosomes from PCa cells to human umbilical vein endothelial cells (HUVECs). In addition, exosomal PGAM1 could bind to γ-actin (ACTG1), which promotes podosome formation and neovascular sprouting in HUVECs. In vivo results revealed exosomal PGAM1 enhanced lung metastasis in nude mice injected with PCa cells via the tail vein. In summary, exosomal PGAM1 promotes angiogenesis and could be used as a liquid biopsy marker for PCa metastasis.


Subject(s)
Exosomes , MicroRNAs , Prostatic Neoplasms , Animals , Humans , Male , Mice , Actins/metabolism , Cell Line, Tumor , Cell Proliferation , Endothelial Cells/metabolism , Exosomes/metabolism , Mice, Nude , MicroRNAs/metabolism , Neoplasm Metastasis/pathology , Phosphoglycerate Mutase/genetics , Phosphoglycerate Mutase/metabolism , Prostatic Neoplasms/pathology
3.
Cell Death Dis ; 12(2): 138, 2021 02 01.
Article in English | MEDLINE | ID: mdl-33542227

ABSTRACT

The interaction between LncRNA and RNA-binding protein (RBPs) plays an essential role in the regulation over the malignant progression of tumors. Previous studies on the mechanism of SNHG1, an emerging lncRNA, have primarily focused on the competing endogenous RNA (ceRNA) mechanism. Nevertheless, the underlying mechanism between SNHG1 and RBPs in tumors remains to be explored, especially in prostate cancer (PCa). SNHG1 expression profiles in PCa were determined through the analysis of TCGA data and tissue microarray at the RNA level. Gain- and loss-of-function experiments were performed to investigate the biological role of SNHG1 in PCa initiation and progression. RNA-seq, immunoblotting, RNA pull-down and RNA immunoprecipitation analyses were utilized to clarify potential pathways with which SNHG1 might be involved. Finally, rescue experiments were carried out to further confirm this mechanism. We found that SNHG1 was dominantly expressed in the nuclei of PCa cells and significantly upregulated in PCa patients. The higher expression level of SNHG1 was dramatically correlated with tumor metastasis and patient survival. Functionally, overexpression of SNHG1 in PCa cells induced epithelial-mesenchymal transition (EMT), accompanied by down-regulation of the epithelial marker, E-cadherin, and up-regulation of the mesenchymal marker, vimentin. Increased proliferation and migration, as well as accelerated xenograft tumor growth, were observed in SNHG1-overexpressing PCa cells, while opposite effects were achieved in SNHG1-silenced cells. Mechanistically, SNHG1 competitively interacted with hnRNPL to impair the translation of protein E-cadherin, thus activating the effect of SNHG1 on the EMT pathway, eventually promoting the metastasis of PCa. Our findings demonstrate that SNHG1 is a positive regulator of EMT activation through the SNHG1-hnRNPL-CDH1 axis. SNHG1 may serve as a novel potential therapeutic target for PCa.


Subject(s)
Antigens, CD/metabolism , Cadherins/metabolism , Gene Expression Regulation, Neoplastic/genetics , Prostatic Neoplasms/genetics , RNA, Long Noncoding/metabolism , Humans , Male , Neoplasm Metastasis , Prostatic Neoplasms/pathology
4.
Oncol Lett ; 16(4): 5160-5166, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30250582

ABSTRACT

Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) has been reported to be overexpressed in prostate cancer cells and associated with tumorigenesis in various types of cancer. However, the biological function of lncRNA PVT1 remains largely unknown. The aim of the present study was to investigate the effect of lncRNA PVT1 expression on the proliferation and migration of prostate cancer cells. Stably transfected prostate cancer cells with downregulated expression of lncRNA PVT1 were constructed by an efficient siRNA fragment, followed by confirmation by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Proliferation was assessed using CCK-8, colony formation and xenograft assays, and cell migration was evaluated using a wound healing assay. The PathScan® Intracellular Signaling Array kit was utilized to explore the underlying molecular mechanisms of lncRNA PVT1 expression in prostate cancer cells. RT-qPCR results confirmed that the lncRNA PVT1 expression level was successfully knocked down in prostate cancer cells. When lncRNA PVT1 expression was downregulated in prostate cancer cells, proliferation and migration were significantly inhibited, compared with the control lncRNA PVT1 group. Furthermore, PVT1 knockdown decreased the phosphorylation of p38 in DU145 cells. Therefore, the present study demonstrated that lncRNA PVT1 downregulation inhibits the proliferation and migration of prostate cancer cells, and is associated with p38 phosphorylation.

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