Diverse roles of SERPINE1 in regulating cellular proliferation and invasion
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ABSTRACT:
PROVIDER: PRJNA1282578 | ENA |
REPOSITORIES: ENA
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Project description:SERPINE1 is involved in various biological processes, but its roles in promoting or suppressing tumorigenesis remain controversial. To understand the underlying mechanisms, we focused on the effects of SERPINE1 downregulation on cell phenotypes, particularly proliferation and invasion, across three types of tumors. High SERPINE1 levels in breast cancer (BRCA) and low-grade glioma (LGG) were associated with poor prognosis. In contrast, elevated SERPINE1 levels in skin cutaneous melanoma (SKCM) correlated with better outcomes. SERPINE1 knockdown resulted in increased xenograft growth in the melanoma cell line C918. This was characterized by the promotion of the cell cycle through the modulation of minichromosome maintenance protein expression and the activity of p53 and SMAD3. In breast cancer cells (MDA-MB-231) with SERPINE1 knockdown, there was decreased xenograft growth and cell proliferation, attributed to a reduction in the uPAR-mediated ERK/p38 activity ratio. With SERPINE1 knockdown, both C918 and MDA-MB-231 cells demonstrated reduced invasion capabilities, decreased matrix metalloproteinase (MMP) activity, and reduced lung metastasis. In low-grade glioma cells (H4), SERPINE1 knockdown led to decreased cell proliferation due to a reduction in the HSP90-mediated ERK/p38 activity ratio. However, it increased invasion and MMP activity, particularly of MMP-1, regulated by the HSP90-p38 axis. Collectively, our findings reveal that SERPINE1 exerts diverse effects on cell proliferation and invasion through context-dependent mechanisms. These results suggest that targeting SERPINE1 may offer personalized therapeutic strategies to enhance treatment precision and reduce adverse effects.
2025-07-03 | GSE300877 | GEO
Project description:The clinical outcomes of hepatocellular carcinoma (HCC) remain dismal. Elucidating the molecular mechanisms for the progression of aggressive HCC holds the promise for developing novel intervention strategies. The transactivation response element RNA-binding protein (TRBP/TARBP2), a key component of microRNA (miRNA) processing and maturation machinery has exhibited to play conflicting roles in tumor development and progression. We sought to investigate the expression of TARBP2 in HCC using well-characterized HCC cell lines, patient-derived tissues and blood samples. Additionally, the potential prognostic and diagnostic value of TARBP2 in HCC were analyzed using Kaplan-Meier plots and ROC curve. Cell counting kit‐8 (CCK‐8), wound healing and transwell assays examined the ability of TARBP2 to induce cell proliferation, migration, and invasion in HCC cell lines. RNA sequencing was applied to identify the downstream elements of TARBP2. The interaction of potential targets of TARBP2, miR‐145 and serpin family E member 1 (SERPINE1), was assessed using luciferase reporter assay. TARBP2 expression was down-regulated in HCC cell lines relative to normal hepatocyte cells, with a similar pattern further confirmed in tissue and blood samples. Notably, the loss of TARBP2 was demonstrated to promote proliferation, migration, and invasion in HCC cell lines. Interestingly, the reduction of TARBP2 was shown to result in the upregulation of SERPINE1, also known as plasminogen activator inhibitor (PAI-1), which is a vital gene of the HIF-1 signaling pathway. Knockdown of SERPINE1 rescued the TARBP2-lost phenotype. Moreover, TARBP2 depletion induced the upregulation of SERPINE1 through reducing the processing of miR-145, which directly targets SERPINE1. Finally, overexpression of miR-145 repressed SERPINE1 and rescued the functions in sh-TARBP2 HCC cells. Our findings underscore a linear TARBP2-miR-145-SERPINE1 pathway that drives HCC progression, with the potential as a novel intervention target for aggressive HCC.
2021-05-26 | GSE143551 | GEO
Project description:Serpine1 mRNA is abundantly induced during EMT. Paradoxically, this mRNA is enriched in the RISC complex, blocking its translation and acting as an endogenous RNA competitor for several miRNAs. Cells that overexpress Serpine1 mRNA have a greater capacity for migration, invasiveness, and resistance to anoikis. These cells show an altered proteomic profile, highlighting the increased levels of expression of the splicing factor TRA2b. This splicing factor is posttranscriptionally regulated during EMT by upregulation of Serpine1 mRNA and the resulting sequestration of miR-130b-5p by this mRNA, which contains three binding sites for miR-130b-5p. Through transcriptomic analysis, we confirmed that Serpin 1 mRNA expression modulates the expression of numerous genes, most of which (>60%) are also modulated by TRA2b overexpression.
2023-12-15 | GSE221152 | GEO
Project description:Serpine1 mRNA is abundantly induced during EMT. Paradoxically, this mRNA is enriched in the RISC complex, blocking its translation and acting as an endogenous RNA competitor for several miRNAs. Cells that overexpress Serpine1 mRNA have a greater capacity for migration, invasiveness, and resistance to anoikis. These cells show an altered proteomic profile, highlighting the increased levels of expression of the splicing factor TRA2b. This splicing factor is posttranscriptionally regulated during EMT by upregulation of Serpine1 mRNA and the resulting sequestration of miR-130b-5p by this mRNA, which contains three binding sites for miR-130b-5p. Through transcriptomic analysis, we confirmed that Serpin 1 mRNA expression modulates the expression of numerous genes, most of which (>60%) are also modulated by TRA2b overexpression.
2023-12-15 | GSE221076 | GEO
Project description:To determine the function of Serpine1 in alveolar cells, the Serpine1 overexpression plasmid pCI-neo-Serpine1 was constructed and transfected into MLE-12 cells
2022-10-05 | GSE212689 | GEO
Project description:This purpose of this experiment was to investigate the transcriptional differences between C57BL6, TIMP1 and Serpine1 knock-out mice infected with SARS MA15 virus. Overview of Experiment: Groups of 20 week old C57BL6, TIMP1 and Serpine1 (PAI1) knock-out mice were infected with SARS MA15 virus. Infections were done at 10^4 PFU or time-matched mock infected. Time points were 4 and 7 d.p.i. There were 2-4 animals/dose/time point. Lung samples were collected for virus load, transcriptional and proteomics analysis. Weight loss and animal survival were also monitored.
2014-02-20 | E-GEOD-51386 | biostudies-arrayexpress
Project description:Chemotherapy resistance remains a major obstacle to eradicating metastatic cancer cells in distant organs. We identified that endothelial cells (ECs) in the lungs, where breast cancer cells often metastasize, form a chemoresistant perivascular niche for disseminated breast cancer cells. By investigating the lung EC secretome activated by metastasis, we found that serine protease inhibitor family E member 1 (SERPINE1), encoded by Serpine1, is upregulated in metastasis-associated lung ECs. This upregulation shields cancer cells from paclitaxel-induced apoptosis and promotes cancer stem cell properties. Serpine1 expression appears to be driven by YAP-TEAD activation in lung ECs that lose cell-cell contact, a phenomenon associated with increased vascular permeability in lungs affected by metastasis. Crucially, pharmacological inhibition of SERPINE1 enhances the chemotherapy sensitivity of metastatic breast cancer cells in the lung. Overall, our findings underscore the pivotal role of the vascular niche, which produces SERPINE1, in conferring chemoresistance to breast cancer cells during metastatic progression in the lungs.
2025-06-16 | GSE279486 | GEO
Project description:Cancer-associated fibroblasts (CAFs) are known to be involved in the progression of various cancers. However, the roles of CAFs in the esophageal squamous cell carcinoma (ESCC) microenvironment remain unclear. We previously co-cultured human bone marrow-derived mesenchymal stem cells (MSCs) with ESCC cells and confirmed the induction of fibroblast activation protein (FAP) in MSCs, which we defined as CAF-like cells. To investigate the roles of CAFs, we performed cDNA microarray analysis between MSCs and CAF-like cells and found that SERPINE1 was highly expressed in CAF-like cells when compared to MSCs. Plasminogen activator inhibitor-1 (PAI-1), encoded by SERPINE1, is generally accepted to play tumor promoting roles and act as a poor prognostic indicator in several cancers. PAI-1 derived from CAF-like cells promoted the cell migration and invasion of ESCC cells by activating Akt and Erk1/2 signaling pathways via low-density lipoprotein receptor related protein 1 (LRP1), the receptor of PAI-1. The higher expression levels of PAI-1 and LRP1 were correlated with the poor prognosis in ESCC patients. These results suggest that PAI-1/LRP1 axis contributes to the progression of ESCC.
2020-07-01 | GSE143138 | GEO
Project description:This purpose of this experiment was to investigate the transcriptional differences between C57BL6, TIMP1 and Serpine1 knock-out mice infected with SARS MA15 virus.
2014-02-20 | GSE51386 | GEO
Project description:By the LC-MS/MS analysis, we identified the proteins that bind to SERPINE1.
2024-04-06 | PXD047066 | Pride