Abstract

Exosomes carrying microRNAs (miRNAs) mediate cell-to-cell communication, which play important roles in cancer growth and progression. However, the roles and molecular mechanisms of the miRNAs in the exosomes from carcinoma-associated fibroblasts (CAFs) are still not clear. The miRNA array showed that miR-3613-3p was an upregulated miRNA in CAFs exosomes. It was verified that miR-3613-3p was upregulated in exosomes from fibroblasts educated by TGF-β1 and the fibroblasts from breast cancer tissues. Exosomal miR-3613-3p promoted breast cancer cell proliferation and metastasis. The cellular functions showed that miR-3613-3p downregulation in the CAFs exosomes suppressed cell proliferation and metastasis in breast cancer by targeting SOCS2 expression. The clinical data showed that miR-3613-3p levels were negatively related to SOCS2 expression in breast cancer tissues. In a conclusion, the study demonstrated that activated fibroblasts exosomes with high levels of miR-3613-3p played an oncogenic role in breast cancer cell survival and metastasis, which suggested that miR-3613-3p function as a therapeutic target.

Highlights

  • Background Exosomes carryingmicroRNA mediate cell to cell communication which are important regulators in cancer growth and progression

  • It was verified that miR-3613-3p was up-regulated in exosomes from fibroblasts educated by TGFβ1, breast cancer cells and breast cancer tissues

  • These findings demonstrated that activated fibroblasts exosomes with high levels of miR3613-3p played an oncogenic role in breast cancer cell survival, metastasis and drug responses, which suggested that the oncogenic role of miR-3613-3p in breast cancer progression

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Summary

Introduction

MicroRNA (miRNAs) mediate cell to cell communication which are important regulators in cancer growth and progression. The roles and molecular mechanism of the miRNAs in the exosomes from carcinoma associated fibroblasts (CAFs) are still not clear. Carcinoma associated fibroblasts (CAFs) are the most prominent cell type in stroma, which build a permissive and supportive microenvironment for tumor development by interacting with cancer cells and other type of cells such as endothelial cells, macrophages [3,4,5]. There are some reports verifying that low levels of exosomes miRNAs from CAFs led to cancer progression such as miR-3188, miR-139 [11,12]. The previous reports indicated that fibroblasts exosomes play important roles in cancer development and progression. The roles and molecular mechanisms of exosomes from CAFs on breast cancer cells are still largely unraveled

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