miR-193a-3p interaction with HMGB1 downregulates human endothelial cell proliferation and migration

Khoo, Cheen P.; Roubelakis, Maria G.; Schrader, Jack B.; Tsaknakis, Grigorios; Konietzny, Rebecca; Kessler, Benedikt M.; Harris, Adrian L.; Watt, Suzanne M.

doi:10.1038/srep44137

Cited by 40 publications

(33 citation statements)

References 75 publications

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“…HMGB1 has been reported to exert multiple cardioprotective effects 51 . Interestingly, although HMGB1 mediated I/R-induced cell migration, which is consistent with previous studies of HMGB1 and cell migration 52 – 54 , HMGB1 did not have an effect on cell viability. However, contradictory reports have been published regarding the role of HMGB1 in apoptosis in different cell types.…”

Section: Discussionsupporting

confidence: 91%

MCPIP1-induced autophagy mediates ischemia/reperfusion injury in endothelial cells via HMGB1 and CaSR

Xie

Zhu

Chen

et al. 2018

Sci Rep

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Monocyte chemotactic protein-1-induced protein 1 (MCPIP1) plays a important role in ischemia/ reperfusion (I/R) injury. Autophagy is involved in activating endothelial cells in response to I/R. However, researchers have not clearly determined whether MCPIP1 mediates I/R injury in endothelial cells via autophagy, and its downstream mechanism remains unclear. Western blotting analyses and immunocytochemistry were applied to detect protein levels were detected in HUVECs. An in vitro scratch assay was used to detect cell migration. Cells were transfected with siRNAs to knockdown MCPIP1 and high mobility group box 1 (HMGB1) expression. The pharmacological activator of autophagy rapamycin and the specific calcium-sensing receptor (CaSR) inhibitor NPS-2143 were used to confirm the roles of autophagy and CaSR in I/R injury. I/R induced HMGB1 and CaSR expression, which subsequently upreguated the migration and apoptosis of HUVECs and coincided with the increase of autophagy. HMGB1 was involved in cell migration, whereas CaSR specifically participated in I/R-induced HUVEC apoptosis. Based on these findings, I/R-induced MCPIP1 expression regulates the migration and apoptosis of HUVECs via HMGB1 and CaSR, respectively, suggesting a new therapeutic targetof I/R injury.Vascular endothelial cell dysfunction plays an crucial role in ischemia/reperfusion (I/R) injury, a common aspect of cardiovascular disease that is characterized by the over-production of inflammatory factors, such as cytokines and chemokines 1,2 . Various biological events, such as autophagy, endoplasmic reticulum stress (ERS) and ubiquitination, are involved in endothelial cell dysfunction. Autophagy plays an important role in the ability of cells to adapt to changing environmental conditions and in cellular remodeling during angiogenesis [3][4][5][6] . However, the mechanisms underlying I/R-induced endothelial cell dysfunction that are associated with autophagy remain poorly understood.Based on accumulating evidence, monocyte chemotactic protein-1 (MCP-1) and its downstream molecule MCP-1-induced protein 1 (MCPIP1) facilitate vascular inflammation and endothelial dysfunction in response to I/R 1, [7][8][9][10] . For example, MCPIP1 has been shown to induce angiogenesis during placental vasculogenesis, which in turn leads to vascular remodeling [11][12][13] . Interestingly, recent studies have linked MCP-1/MCPIP1 with autophagy under different conditions that induce cell activation and apoptosis. For instance, MCP-1 and MCPIP1 contribute to cardiomyoblast death in patients with heart failure and are associated with autophagy resulting from ERS 14 . Moreover, MCPIP1-induced autophagy is required for angiogenesis in patients with angiogenesis-related cardiovascular diseases 15 . On the other hand, MCPIP1/p53 expression is induced after SiO2 exposure and promotes macrophage activation and apoptosis, suggesting the presence of a general link between the MCPIP1 signaling pathway and autophagy in different diseases 16,17 .

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Section: Discussionsupporting

confidence: 91%

MCPIP1-induced autophagy mediates ischemia/reperfusion injury in endothelial cells via HMGB1 and CaSR

Xie

Zhu

Chen

et al. 2018

Sci Rep

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“…Concerning its role in cell physiology, the main available data were obtained from studies on the following: (a) cord-blood and peripheral blood endothelial colony-forming cells (CB/PB-ECFC) derived from donations of healthy subjects; (b) from skeletal muscle specimens of control subjects (CTRL) with no sign of muscle pathology detectable by immunohistochemistry; and (c) from endometrial epithelial cells of healthy volunteer women aged 18 through 36 years old. In particular, it has been found that miR-193a-3p was one of the 25 miRNAs differentially regulated in CB-ECFC versus PB-ECFC [ 21 ]. It was highly expressed in the less-proliferative PB-ECFCs where its inhibition using anti-miR molecules improved the in vitro proliferation, migration, and vascular tubule formation of these cells.…”

Section: Biological Function Of Mir-193a-3p In Development and In mentioning

confidence: 99%

Biological Function of MicroRNA193a-3p in Health and Disease

Grossi

Salvi

Abeni

et al. 2017

International Journal of Genomics

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MicroRNAs (miRNAs) are a class of small noncoding RNAs that act mainly as negative regulators of gene expression. Several studies demonstrated that miRNAs take part in numerous biological processes, such as proliferation, apoptosis, and migration. The dysregulation of miRNAs has been frequently observed in different types of disease, including cancer. Here, we provide a comprehensive review on the human miR-193a-3p by considering its role in both physiological and pathological contexts. Different mechanisms involved in regulating miR-193a-3p expression have been reported, including epigenetic modifications and transcription factors. In physiological contexts, miR-193a-3p seemed able to limit proliferation and cell cycle progression in normal cells. Remarkably, several publications demonstrated that miR-193a-3p acted as a tumor suppressor miRNA in cancer by targeting different genes involved in proliferation, apoptosis, migration, invasion, and metastasis. Furthermore, the downregulation of miR-193a-3p has been observed in many primary tumors and altered levels of circulating miR-193a-3p have been identified in serum or plasma of cancer patients and subjects affected by Parkinson's disease or by schizophrenia. In a clinical perspective, further studies are needed to explore the antitumor effects of the miR-193a-3p mimics delivery and the relevance of this miRNA detection as a possible diagnostic and prognostic biomarker.

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“…CyQuant cell proliferation assay assesses proliferation by quantifying total cellular DNA content [ 21 – 23 ]. Synchronized MO7e 10,000 cells/well were seeded in a 96 well white plate and incubated with S at 40ng/mL and N at 40μM respectively in complete medium for 24h.…”

Section: Methodsmentioning

confidence: 99%

Stem cell factor and NSC87877 combine to enhance c-Kit mediated proliferation of human megakaryoblastic cells

2018

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Enhancement of hematopoietic stem cells (HSCs) proliferation is a central aim in bone marrow transplantation (BMT). A stem cell factor (SCF) and c-Kit mediated extracellular signaling trigger proliferation of HSCs. This signaling is negatively regulated by protein tyrosine phosphatases (PTPs), SHP-1 and SHP-2. Although NSC87877 (N) is known to inhibit SHP-1/SHP-2, c-Kit-mediated HSCs proliferation by inhibiting SHP-1/SHP-2 has not been reported. This study investigated the combined effect of SCF (S) and N in c-Kit mediated proliferation and underlying mechanisms. The growth of human megakaryoblastic cell line, MO7e and HSCs, upon treatment with S and N alone, and in combination was assessed by PrestoBlue staining. The expression of c-Kit, phosphorylated c-Kit, SHP-1/SHP-2 and HePTP inhibition using S and N treatment were evaluated in the MO7e cells. Megakaryoblast cell proliferation was determined by quantification of Ki-67+, S-phase, BrdU+ and CFDA-SE+ cells using flow cytometry. The combination of S and N leads to enhanced cell growth compared with either S or N alone. Collectively, the results reveal a novel mechanism by which S in combination with N significantly enhances proliferation of human megakaryoblast cells. The pretreatment of N before S enhances proliferation of cells than S alone. This promising combination would likely play an essential role in enhancing the proliferation of cells.

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miR-193a-3p interaction with HMGB1 downregulates human endothelial cell proliferation and migration

Cited by 40 publications

References 75 publications

MCPIP1-induced autophagy mediates ischemia/reperfusion injury in endothelial cells via HMGB1 and CaSR

MCPIP1-induced autophagy mediates ischemia/reperfusion injury in endothelial cells via HMGB1 and CaSR

Biological Function of MicroRNA193a-3p in Health and Disease

Stem cell factor and NSC87877 combine to enhance c-Kit mediated proliferation of human megakaryoblastic cells

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