Endothelial cells require miR-214 to secrete exosomes that suppress senescence and induce angiogenesis in human and mouse endothelial cells

Abstract

Key Points Endothelial cells secrete exosomes containing miR-214, which suppress senescence and stimulates an angiogenic program in target cells. Exosomal miR-214 regulates ataxia telangiectasia mutated expression in recipient endothelial cells.

Extracellular vesicles swarm the cancer microenvironment: from tumor–stroma communication to drug intervention

“…For example, leukemia-derived EVs can induce a CAF phenotype in stromal cells in the surrounding microenvironment, hence leading to increased expression of pro-angiogenic factors in such cells 40,60 . Finally, EV-mediated crosstalk occurs also between endothelial cells themselves 79 .…”

Involvement of microRNA214 and transcriptional regulation in reductions in mevalonate pyrophosphate decarboxylase mRNA levels in stroke-prone spontaneously hypertensive rat livers

“…Exosomes are small membrane vesicles of an endosomal origin that are secreted into the extracellular compartment by exocytosis. 50) Exosomes consist of a limiting lipid bilayer, transmembrane proteins, and a hydrophilic core containing proteins, mRNAs, and miRs. Endothelial cells were previously shown to require miR-214 to secrete exosomes.…”

Future directions of extracellular vesicle-associated miRNAs in metastasis

“…Therefore, additional miRNA loaded EV studies in different cancer cell types will widen the understanding of this cancer progression mechanism. On the other hand, it is shown in Dhondt et al 's review that oncomirs loaded in exosomes of primary tumors or metastasis cells favor the metastasis process for example preparing other tissues niches like exosomes carrying miR-105 secreted by breast metastatic cancer cells and internalized by endothelial cells (11); favoring angiogenesis like miR-214 found in exosomes of epithelial cells (12); inducing migration by miR-409 from cancer associated fibroblasts in EV (13); stimulating invasion by mir-105 found in breast cancer cell exosomes (11); promoting proliferation like miR-429 in hepatocellular carcinoma (14); potentiating invasive and adhesive capabilities as miR-210 in brain metastasis competent cell-derived exosomes (15); triggering epithelial to mesenchymal transformation by miR-409 from cancer associated fibroblasts in EV (16) and miR-221 in extra-hepatic cholangiocarcinoma (17); or additionally, participating in mesenchymal to epithelial transition (18). These results direct to the question: how do cells tag a type of miRNA to be discarded or used to enhance cancer traits?…”