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

Overview

Journal Cancer Cell Int

Publisher Biomed Central

Date 2022 Apr 19

PMID 35436935

Authors

Yuwei Shou

Xiaoqian Wang

Chao Chen

Yinghao Liang

Chenbo Yang

Qiankun Xiao

Hui Li

Shuaiyuan Wang

Jiao Shu

Xiangyu Tian

Kuisheng Chen

Affiliations

Soon will be listed here.

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 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 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.

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