MicroRNA-135b acts as a tumor promoter by targeting the hypoxia-inducible factor pathway in genetically defined mouse model of head and neck squamous cell carcinoma

Here in, we investigated the mechanism underlying overexpression of miR-135b in the human head and neck squamous cell carcinoma (HNSCC) cell lines and in the HNSCC mouse model. Exogenous expression of miR-135b in these cell lines increased cell proliferation, migration, and colony formation. Gene silencing analysis revealed that miR-135b affects a regulator that inhibits hypoxia-inducible factor (HIF). Increased miR-135b expression was positively correlated with HIF-1α expression and microvessel density in the HNSCC model. Thus, our data demonstrate that miR-135b acts as a tumor promoter by promoting cancer cell proliferation, colony formation, survival, and angiogenesis through activation of HIF-1α in HNSCC.

► Spontaneous development of HNSCC in Tgfbr1/Pten 2cKO mice results in miR-135b overexpression. ► The oncogenic potential of increased miR-135b expression mainly correlates to Tgfbr1 deletion. ► miR-135b promotes angiogenesis potential of HUVEC in HNSCC mice. ► miR-135b decreases FIH expression and increases expression of HIF-1α and VEGFA in HNSCC.