Dataset Information

MiR-765 induces angiogenesis by inhibiting dipeptidyl peptidase 4 and increasing fibroblast growth factor 2

ABSTRACT: Given that extracellular vesicles (EVs) secreted from stem cells contain angiogenic microRNAs (miRNAs), these EVs show equivalent angiogenic therapeutic effect to cell transplantation. This study aimed to identify the angiogenic miRNAs from several miRNAs involved in EVs secreted from stem cells. In human dental pulp stem cells (hDPSCs) under hypoxic culture, vascular endothelial growth factor (VEGF) involved in EVs increased. We hypothesized that angiogenic miRNAs increase in EVs that are secreted from hDPSCs under hypoxic culture compared with those under normoxic culture. In the first screening, the expression levels of miRNAs involved in EVs that were secreted from hDPSCs cultured under hypoxic and normoxic conditions were analyzed using miRNA array. In the second screening, 12 miRNAs were individually involved in EVs, and the growth of human aortic endothelial cells was assayed. In the third screening, miRNA-encapsulated EVs were injected in BALB/c mouse hindlimb ischemia model, followed by angiogenesis evaluation by blood flow analysis. Results showed that miR-765 is an angiogenic miRNA, targeting the 3′ untranslated region of dipeptidyl peptidase 4 (DPP4) and upregulating fibroblast growth factor 2 (FGF2) in vitro and in vivo. In conclusion, as an angiogenesis mechanism, miR-765 increased FGF2 expression levels by inhibiting DPP4.

ORGANISM(S): Homo sapiens

PROVIDER: GSE232178 | GEO | 2024/05/08

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Malignant germ-cell-tumours (GCTs) are characterised by microRNA (miRNA/miR-) dysregulation, with universal over-expression of miR-371~373 and miR-302/367 clusters regardless of patient age, tumour site, or subtype (seminoma/yolk-sac-tumour/embryonal carcinoma). These miRNAs are released into the bloodstream, presumed within extracellular-vesicles (EVs) and represent promising biomarkers. Here, we comprehensively examined the role of EVs, and their miRNA cargo, on (fibroblast/endothelial/macrophage) cells representative of the testicular GCT (TGCT) tumour microenvironment (TME). Small RNA next-generation-sequencing was performed on 34 samples, comprising representative malignant GCT cell lines/EVs and controls (testis fibroblast [Hs1.Tes] cell-line/EVs and testis/ovary samples). TME cells received TGCT co-culture, TGCT-derived EVs, and a miRNA overexpression system (miR-371a-OE) to assess functional relevance. TGCT cells secreted EVs into culture media. MiR-371~373 and miR-302/367 cluster miRNAs were overexpressed in all TGCT cells/subtypes compared with control cells and were highly abundant in TGCT-derived EVs, with miR-371a-3p/miR-371a-5p the most abundant. TGCT co-culture resulted in increased levels of miRNAs from the miR-371~373 and miR-302/367 clusters in TME (fibroblast) cells. Next, fluorescent labelling demonstrated TGCT-derived EVs were internalised by all TME (fibroblast/endothelial/macrophage) cells. TME (fibroblast/endothelial) cell treatment with EVs derived from different TGCT subtypes resulted in increased miR-371~373 and miR-302/367 miRNA levels, and other generic (eg, miR-205-5p/miR-148-3p) and subtype-specific (seminoma, eg, miR-203a-3p; yolk-sac-tumour, eg, miR-375-3p) miRNAs. MiR-371a-OE in TME cells resulted in increased collagen contraction (fibroblasts) and angiogenesis (endothelial cells), via direct mRNA downregulation and alteration of relevant pathways. TGCT cells communicate with nontumour stromal TME cells through release of EVs enriched in oncogenic miRNAs, potentially contributing to tumour progression.

Dataset Information

MiR-765 induces angiogenesis by inhibiting dipeptidyl peptidase 4 and increasing fibroblast growth factor 2

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets