Loss of microRNA-30e induced by extracellular vesicles from cancer-associated fibroblasts promotes breast cancer progression by binding to CTHRC1.

Abstract Breast cancer (BC) is a frequently occurring malignancies within female population. Recently, the significance of extracellular vesicles (EVs) derived from cancer-associated fibroblasts (CAF) (CAF-EVs) in malignancies has been increasingly recognized. The study aims to explore the functional mechanism of CAF-EVs in the development of BC. Initially, EVs were isolated from CAF, followed by observation on morphological change using transmission electronic microscope. Next, BC and the adjacent normal tissues were collected for quantification of microRNA (miR)-30e and collagen triple helix repeat containing 1 (CTHRC1) using RT-qPCR and Western blot analysis. miR-30e was downregulated in BC, while CTHRC1 was upregulated. Luciferase assay revealed that miR-30e targeted CTHRC1. miR-30e and CTHRC1 expression was altered to evaluate their effects on BC cell viabilities in vitro. It was shown that overexpression of miR-30e or silencing of CTHRC1 suppressed proliferation, migration/invasion of BC cells but promoted apoptosis. Xenograft tumors were developed in mice to observe the tumorigenesis. To sum up, CAF-EVs reduced miR-30e expression to upregulate CTHRC1, which aggravated BC in vitro and in vivo.