Exosomal miR16 induced by allyl isothiocyanate (AITC) inhibits tumor growth in cervical cancer via modulation of apoptotic and inflammatory pathways
The tumor micro-environment is a key determinant for promoting cancer cell growth and development with exosomal miRNAs emerging as key regulators of tumor growth and metastasis. miR16 is one well-established tumor suppressor miRNAs that induces apoptosis, while inhibiting angiogenesis and inflammation across various cancers. Herein, we investigated the role of exosomal miR16 in the cervical cancer microenvironment and its underlying molecular mechanisms. We treated human cervical cancer HeLa cells with Allyl Isothiocyanate (AITC) and observed the impact of miR16-enriched exosomes on human fibrosarcoma HT1080 cells. We found a significant increase of miR16 expression in AITC-treated HeLa cells and purified exosomes. When the exosomes were cultured with fibroblasts, miR16 expression was increased in fibroblast cells. Treatment with AITC-exposed HeLa exosomes induced increased Bax/Bcl2 ratio and downregulated PCNA, HIF-1α, SDF-1α, IL-6, and p22phox expression in fibroblasts. Remarkably, the knockdown of miR16 in fibroblasts inhibited the AITC-induced increase in the Bax/Bcl2 ratio and restored VEGF, PCNA, HIF-1α, SDF-1α, IL-6, and p22phox expression. In sum, our findings demonstrate the potential of AITC-mediated exosomal miR16 enrichment as an effective approach to inhibit cancer growth and development, and reveal a new potential for cancer management and therapy.