MicroRNA-21 promotes head and neck squamous cell carcinoma (HNSCC) induced transition of bone marrow mesenchymal stem cells to cancer-associated fibroblasts.

ABSTRACT

BACKGROUND: Most patients diagnosed with head and neck tumor will present with locally advanced disease, requiring multimodality therapy. Bone marrow-derived mesenchymal stromal cells (BMSCs) respond to a variety of tumor cell-derived signals, such as inflammatory cytokines and growth factors. As a result, the inflammatory tumor microenvironment may lead to the recruitment of BMSCs. Whether BMSCs in the tumor environment are more likely to promote tumor growth or tumor suppression is still controversial. We aimed to determine whether microRNA-21(miR-21) would play a vital role in HNSCC induced transition of human bone marrow mesenchymal stem cells (hBMSCs) to cancer-associated fibroblasts (CAFs). METHODS: In this study, we used electron microscope to observed exosomes collected from human tissue and two cell lines. We co-cultured hBMSCs with exosomes from FaDu and Cal-27 cells with miR-21 inhibited or not, then assessed cell cycle changes of hBMSCs with flow cytometry and determined expression level of α-SMA and FAP through qRT-PCR and Western blot. RESULTS: We observed an up-regulation of miR-21 expression in HNSCC tissue and FaDu and Cal-27 cells. Importantly, the exosomes derived from both cells induced CAFs-like characteristics in hBMSCs. while treatment with a miR-21 inhibitor effectively suppressed the transition of hBMSCs to CAFs and reversed the changes in the cell cycle distribution. This suggests that miR-21 plays a crucial role in facilitating the transition of hBMSCs to CAFs and modulating the cell cycle dynamics. CONCLUSION: Our findings highlight the significance of miR-21 in mediating the communication between HNSCC cells and hBMSCs through exosomes, leading to the promotion of CAFs-like features and alterations in the cell cycle of hBMSCs.