Abstract
Background Exosomes carrying microRNA (miRNAs) mediate cell to cell communication which are important regulators in cancer growth and progression. However, the roles and molecular mechanism of the miRNAs in the exosomes from carcinoma associated fibroblasts (CAFs) are still not clear. Methods The targeted gene of miR-3613-3p was predicted by TargetScan and miRanda. The proliferation of cancer cells was conducted by cell counting kit-8 and colony formation assay. Cancer cell migration and invasion were measured by wound healing assay and Transwell assays respectively. Luciferase activity was assayed by dual luciferase assay system. miRNA and mRNA expression was measured by real time RT-PCR. SOCS2 protein levels was assayed by western blotting. Results It was verified that miR-3613-3p was up-regulated in exosomes from fibroblasts educated by TGF-β1, breast cancer cells and breast cancer tissues. Exosomal miR-3613-3p promoted breast cancer cell proliferation and metastasis. Loss-of-function experiments revealed that miR-3613-3p down-regulation in the CAFs exosomes suppressed cell proliferation and drug resistance in breast cancer by targeting SOCS2 expression. The clinical data showed that miR-3613-3p was negatively related to SOCS2 in breast cancer tissues. Conclusion These findings demonstrated that activated fibroblasts exosomes with high levels of miR-3613-3p 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.
Rapamycin antagonizes cadmium-induced breast cancer cell proliferation and metastasis through directly modulating ACSS2
