Extracellular vesicles carrying miR-193a derived from mesenchymal stem cells impede cell proliferation, migration and invasion of colon cancer by downregulating FAK

携带间充质干细胞来源的 miR-193a 的细胞外囊泡通过下调 FAK 抑制结肠癌细胞增殖、迁移和侵袭

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Abstract

MicroRNA (miR) deregulation is frequently seen in colon cancer. In this study, we sought to investigate biological effects of miR-193a on colon cancer and its underlying mechanism. Microarray analysis was conducted to obtain the differentially expressed miRs and their target genes in colon cancer. Bone-marrow derived mesenchymal stem cells (MSCs) and extracellular vesicles (EVs) were obtained. The functional roles of miR-193a and FAK in colon cancer were determined using loss- and gain-function experiments. The cell proliferation, and migration and invasion were evaluated by CCK-8 and Transwell assay respectively. Dual-luciferase reporter assay was performed to confirm the targeting relationship between miR-193a and FAK. Furthermore, in vivo experiment was conducted to test the roles of EV miR-193a in colon cancer growth, followed by determination of PCNA, MMP-2, and MMP-9 protein expression using Western blot analysis. MiR-193a was downregulated, whereas FAK was upregulated in colon cancer. MiR-193a upregulation or FAK downregulation inhibited proliferation, migration and invasion of colon cancer cells. miR-193a could downregulate FAK. Upregulation of EV miR-193a was observed to impede proliferation, migration and invasion of colon cancer cells in vitro and in vivo, accompanied by decreased PCNA, MMP-2, and MMP-9 expression. In summary, EV miR-193a derived from MSCs impeded colon cancer progression by targeting FAK, thus suggesting a new potential strategy for colon cancer treatment.

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