Exosomal miR-301a-3p from esophageal squamous cell carcinoma cells promotes angiogenesis by inducing M2 polarization of macrophages via the PTEN/PI3K/AKT signaling pathway
Exosomal miR-301a-3p from esophageal squamous cell carcinoma cells promotes angiogenesis by inducing M2 polarization of macrophages via the PTEN/PI3K/AKT signaling pathway
Blog Article
Abstract Background Growing evidence has indicated that tumor-associated macrophages (TAMs) promote tumor angiogenesis.However, the mechanisms underlying the pro-angiogenic switch of TAMs remains unclear.Here, we examined how read more exosomal miR-301a-3p secreted by esophageal squamous cell carcinoma (ESCC) cells triggers the pro-angiogenic switch of TAMs.
Methods We quantified miR-301a-3p levels in ESCC tumors using qRT-PCR.Macrophage phenotypes were identified using flow cytometry and qRT-PCR.The pro-angiogenic ability of TAMs was measured using the CCK-8 assay, scratch assay, Transwell migration and invasion assay, and tube formation assay.
The mechanism by which exosomal miR-301a-3p secreted by ESCC cells triggers the pro-angiogenic switch of TAMs was elucidated using western blots, qRT-PCR, and a dual-luciferase reporter assay.Results We observed anomalous miR-301a-3p overexpression in ESCC tumor tissues and cell lines.Then, we verified that ESCC-derived exosomes promoted angiogenesis by inducing macrophage polarization into pentair hose M2 type, and exosomal miR-301a-3p secreted by ESCC cells was responsible for this effect.
Finally, we discovered that exosomal miR-301a-3p promoted M2 macrophage polarization via the inhibition of PTEN and activation of the PI3K/AKT signaling pathway, subsequently promoting angiogenesis via the secretion of VEGFA and MMP9.Conclusion The pro-angiogenic switch of TAMs is triggered by exosomal miR-301a-3p secreted from ESCC cells via the PTEN/PI3K/AKT signaling pathway.Although tumor angiogenesis can be regulated by a wide range of factors, exosomal miR-301a-3p could hold promise as a novel anti-angiogenesis target for ESCC treatment.