The impact of stanniocalcin 1 on the transcriptome of human cord blood stem/progenitors
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE136884 | GEO | 2019/09/05
REPOSITORIES: GEO
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Project description:Stanniocalcin 1 (STC1) plays an integral role in the metastasis of ovarian cancer. However, the functional role of STC1 in lipid metabolism is not fully understood. Single-cell sequencing assays verified that STC1 expression was significantly enhanced in ovarian cancer tissues compared with para-carcinoma tissues, and it was further up-regulated in peritoneal metastasis tissues compared with tumor tissues. In vitro and in vivo experiments demonstrated that STC1 promoted cell proliferation and metastasis by enhancing lipid metabolism. Mechanistically, STC1 directly bound to integrin β6 (ITGB6) and activated the PI3K signaling pathway. Moreover, STC1 was directly regulated by FOXC2 and FOXC2 was up-regulated and positively correlated with STC1 in ovarian cancer. Notably, STC1 knockdown had a synergistic effect with cisplatin (DDP) chemotherapy.Overall, these findings reveal that STC1 increases metastasis by promoting lipid metabolism via the FOXC2/ITGB6 signaling axis and may be a potential target for chemotherapy-resistant ovarian cancer.
2022-04-13 | GSE185833 | GEO
Project description:Although calcific aortic valve stenosis (CAVS) is the most prevalent valvular heart disease, the molecular mechanisms underlying aortic valve calcification remain unknown. Here, we found a significant elevation in stanniocalcin-1 (STC1) expression in the valve interstitial cells (VICs) of calcific aortic valves by combined analysis of our comprehensive gene expression data and microarray datasets reported previously. Immunohistochemical staining showed that STC1 was located around the calcific area in the aortic valves of patients with CAVS. In vitro experiments using inhibitors and small interfering RNA (siRNA) targeting osteoblast differentiation signaling revealed that activation of the Akt/STC1 axis was essential for runt-related transcription factor 2 (RUNX2) induction in the VICs. RNA sequencing and bioinformatics analysis of STC1-knocked down VICs in osteoblast differentiation medium resulted in silencing of the induction of osteoarthritis signaling-related genes, including RUNX2 and COL10A1.
2026-10-01 | GSE226981 | GEO
Project description:Although calcific aortic valve stenosis (CAVS) is the most prevalent valvular heart disease, the molecular mechanisms underlying aortic valve calcification remain unknown. Here, we found a significant elevation in stanniocalcin-1 (STC1) expression in the valve interstitial cells (VICs) of calcific aortic valves by combined analysis of our comprehensive gene expression data and microarray datasets reported previously. Immunohistochemical staining showed that STC1 was located around the calcific area in the aortic valves of patients with CAVS. In vitro experiments using inhibitors and siRNA targeting osteoblast differentiation signaling revealed that activation of the Akt/STC1 axis was essential for runt-related transcription factor 2 (RUNX2) induction in the VICs. RNA sequencing and bioinformatics analysis of STC1-knocked down VICs in osteoblast differentiation medium resulted in silencing of the induction of osteoarthritis signaling-related genes, including RUNX2 and COL10A1. STC1 depletion in the murine CAVS model improved aortic valve dysfunction with high peak velocity and valve thickening and suppressed the appearance of osteochondrocytes. STC1-deficient mice also exhibited complete calcification abolishment, although partial valve thickening by aortic valve injury was observed. Our findings suggest that STC1 may be a critical factor in determining valve calcification and a novel target for preventing the transition to severe CAVS with calcification. We analyzed the gene expression profiles of the valve interstitial cells (VICs) isolated from noncalcific and calcific areas in calcific aortic valve stenosis (CAVS) donors using a gene microarray.
2023-12-31 | GSE226781 | GEO
Project description:Background: Idiopathic pulmonary arterial hypertension (IPAH) is driven by progressive pulmonary vascular remodeling, particularly pulmonary arterial smooth muscle cell (PASMC) proliferation. Current combination vasodilator therapies have markedly improved outcomes; however, prognosis remains poor in subgroups such as patients with respiratory comorbidities, highlighting the need for novel therapies. Elevation of intravascular hydrostatic pressure is a hallmark of IPAH, yet its direct role in PASMC pathobiology remains largely unexplored. We developed a cyclic hydrostatic pressurization culture system to model hypertensive hemodynamic stress in vitro and identify pressure-responsive mediators. Methods: PASMCs from 4 patients with IPAH were exposed to high hydrostatic pressure (70/40 mmHg, 60 bpm). Transcriptomic profiling identified differentially expressed genes, validated by qPCR. Functional studies included piezo-type mechanosensitive ion channel component 1 (PIEZO1) modulation, recombinant human stanniocalcin-1 (rhSTC1) treatment, bromodeoxyuridine (BrdU) incorporation, and western blotting for cell-cycle regulators. In vivo, chronic hypoxia–induced pulmonary hypertension was assessed in wild-type and Stc1–/– mice by hemodynamic and histological analyses, with or without intratracheal rhSTC1 administration. Results: RNA sequencing revealed STC1 as a robustly pressure-induced gene in IPAH PASMCs. PIEZO1 activation upregulated STC1, whereas knockdown blunted this response. Elevated STC1 expression was observed in PASMCs of IPAH lung tissue and rhSTC1 reduced PASMC proliferation and increased p-p53, p21, and p27 expression. In the chronic hypoxia model, Stc1–/– mice exhibited higher right ventricular systolic pressure (RVSP) (43.7 ± 1.3 vs. 30.6 ± 0.9 mmHg) and greater pulmonary arterial medial thickness (39.1 ± 2.5% vs. 26.5 ± 1.3%) than wild-type mice. CD68-positive macrophages were increased in Stc1–/– mice under normoxia and further elevated with hypoxia. In wild-type and Stc1–/– PAH models, intratracheal administration of rhSTC1 markedly reduced medial thickening, and CD68-positive macrophage accumulation, and RVSP in both wild-type and Stc1–/– mice. Conclusions: We demonstrate, for the first time, that elevated hydrostatic pressure drives STC1 expression via PIEZO1, conferring potent anti-remodeling effects in IPAH. STC1 supplementation represents a promising therapeutic strategy that addresses an urgent medical need not fulfilled by conventional therapies.
2026-09-05 | GSE317316 | GEO
Project description:Resistance to temozolomide (TMZ) is one of the major challenges for glioblastoma (GBM) therapy while the underlying mechanisms demand further exploration. Tumor-repopulating cells (TRCs) have been proven to be involved in chemotherapy resistentce. We first enriched GBM TRCs by culturing DBTRG cells in 3D soft fibrin gels and performed RNA-seq. By anlyzing the differentially expressed genes (DEGs) between TRCs and 2D conventionally cultured DBTRG cells, we identified the glycoprotein gene Stanniocalcin-1 (STC1), which is highly expressed in TRCs. Our analyses using patient data from CGGA disclosed that high STC1 expression was associated with poor prognosis, high glioma grade and TMZ therapy resistance. Both our in vitro and in vivo expreriments showed that overexpression of STC1 promoted while knockdown of STC1 inhibited GBM cell proliferation and TMZ resistance. Our mechanistic study revealed that STC1 elevated the phosphoralation of STAT3 to increase MGMT expression, which inhibited the TMZ-induced DNA damage and apoptosis. Our study provides rationale for targeting STC1 to overcome TMZ resistance.
2024-04-30 | GSE261684 | GEO
Project description:The impact of stanniocalcin 1 on the transcriptome of human cord blood stem/progenitors
| PRJNA563915 | ENA
Project description:The clinical benefit of immune checkpoint inhibitor (ICI) treatments in patients with advanced KRAS mutant non-small-cell lung cancer (NSCLC) is limited. Here, we found IBI351, a selective KRASG12C inhibitor, significantly enhanced the efficacy of anti-PD-1 antibody (αPD-1) in inhibiting tumor growth in vitro and in vivo. Mechanistically, IBI351 inhibited STAT3 activity, leading to downregulation of stanniocalcin 1 (STC1). STC1 anchors calreticulin (CRT) to the mitochondrial membrane; its downregulation promoted CRT translocation to the cancer cell surface, increasing the ‘eat me’ signal and enhancing T cell infiltration. In clinical specimens from KRASG12C mutant NSCLC patients treated with PD-1 inhibitors, low STC1 expression correlated with better treatment response and prolonged survival. Together, these findings demonstrate that IBI351 enhances ICI efficacy by suppressing the STAT3-STC1 axis and promoting CRT-mediated phagocytosis, supporting further clinical evaluation of this combination.
2026-06-05 | GSE328294 | GEO
Project description:Evaluation of X-linked gene expression in MEFs isolated from STC1 wild type and knock out mice X chromosome inactivation (XCI) is initiated in cis by the Xist RNA, which coats the inactive X chromosome (Xi) from which it is produced. We performed a large-scale RNA interference screen to identify trans-acting XCI factors (XCIFs) that comprise regulators of cell signaling and transcription. We find that the XCIFs promote Xist expression and/or localization to the Xi. One of the XCIFs, STC1, is a glycoprotein found in both the cytoplasm and nucleus and whose function is poorly understood. A homozygous mouse knockout of STC1 has a defect in XCI but surprisingly is phenotypically normal. We performed transcriptome profiling (RNA-Seq) experiments to determine whether the expression levels of X-encoded genes were elevated in Stc1-/- female MEFs. In these experiments, RNA was prepared from three independent cultures of Stc1+/+ or Stc1-/- female MEFs. RNA samples were processed and amplified followed by deep sequencing. The similarity of X-linked gene expression between Stc1+/+ and Stc1-/- MEFs was statistically significant. The vast majority of autosomal genes were also expressed at comparable levels in Stc1+/+ and Stc1-/- MEFs. Sequenced mRNA isolated from the STC1+/+ or STC1-/- MEFs.
2014-07-29 | E-GEOD-47395 | biostudies-arrayexpress
Project description:Introduction: Donation after circulatory death (DCD) criteria serves as a potential strategy to expand the organ pool for heart transplantation. However, DCD procurement introduces prolonged warm ischemic times that accelerate endothelial and cardiomyocyte injury. Hypothermic oxygenated perfusion (HOPE) has emerged as a novel metabolic preservation strategy, yet its biological mechanisms remain undefined. We investigated how HOPE preservation modulates cardiomyocyte viability and myocardial metabolic stability after DCD in a porcine model. Methods and Results: Following induced circulatory arrest and reperfusion with or without in situ normothermic regional perfusion (NRP), porcine hearts were preserved for 2 hours by static cold storage (SCS) or up to 24 hours by HOPE and reanimated using a ex vivo Langendorff circuit, under normothermic conditions. HOPE preservation maintained myocardial structure, cardiomyocyte viability, and sinus rhythm after 24 hours, sixfold beyond the conventional preservation window. Flow cytometry revealed measurable populations of troponin-positive viable cardiomyocytes after 24-hour HOPE, in contrast to complete loss after 24-hour SCS. RNA sequencing and metabolomics demonstrated minimal transcriptional or metabolic shift between 2-hour SCS and 24-hour HOPE hearts, with preservation of oxidative and glycolytic balance and limited inflammatory activation. In contrast, omission of NRP during procurement resulted in marked loss of contractility and cardiomyocyte integrity, underscoring its potential role in pre-preservation harvest in a porcine model. Conclusions: In a swine model extended hypothermic oxygenated perfusion preservation sustains myocardial and metabolic integrity after circulatory death by minimizing transcriptional and metabolic injury signatures. These findings identify a biologically distinct preservation state that mitigates ischemia-reperfusion injury and may inform novel strategies for organ and tissue preservation.
2026-06-08 | GSE316371 | GEO
Project description:Evaluation of X-linked gene expression in MEFs isolated from STC1 wild type and knock out mice X chromosome inactivation (XCI) is initiated in cis by the Xist RNA, which coats the inactive X chromosome (Xi) from which it is produced. We performed a large-scale RNA interference screen to identify trans-acting XCI factors (XCIFs) that comprise regulators of cell signaling and transcription. We find that the XCIFs promote Xist expression and/or localization to the Xi. One of the XCIFs, STC1, is a glycoprotein found in both the cytoplasm and nucleus and whose function is poorly understood. A homozygous mouse knockout of STC1 has a defect in XCI but surprisingly is phenotypically normal. We performed transcriptome profiling (RNA-Seq) experiments to determine whether the expression levels of X-encoded genes were elevated in Stc1-/- female MEFs. In these experiments, RNA was prepared from three independent cultures of Stc1+/+ or Stc1-/- female MEFs. RNA samples were processed and amplified followed by deep sequencing. The similarity of X-linked gene expression between Stc1+/+ and Stc1-/- MEFs was statistically significant. The vast majority of autosomal genes were also expressed at comparable levels in Stc1+/+ and Stc1-/- MEFs.
2014-07-29 | GSE47395 | GEO