MicroRNA-106b is involved in transforming growth factor beta 1-induced cell migration by targeting disabled homolog 2 in cervical carcinoma

Background: MicroRNA-106b (miR-106b) was recently identified as an oncogene participating in cancer progression. Transforming growth factor beta 1(TGF-beta 1) is an indispensable cytokine regulating the local microenvironment, thereby promoting cervical cancer progression. However, the roles of miR-106b in cervical carcinoma progression and TGF-beta 1-involvement in the tumorigenesis of cervical cancer remain unknown. Methods: The expression of miR-106b in human cervical specimens was detected by real-time PCR analysis and in situ hybridization assay. The effect of miR-106b on cell migration was analyzed by scratch and transwell assays. TGF-beta 1 was used to induce cell migration. The expression of the miR-106b target gene DAB2 in human cervical tissues and cell lines were measured by qRT-PCR, western blot and immunohistochemistry. Dual-luciferase reporter assay was used to identify DAB2 as a miR-106b-directed target gene. Results: miR-106b was frequently up-regulated in human cervical carcinoma specimens and cervical cancer cell lines. Over-expression of miR-106b significantly promoted HeLa and SiHa cells migration. Likewise, inhibition of miR-106b decreased HeLa and SiHa cells migration. The multifunctional cytokine TGF-beta facilitates metastasis in cervical carcinoma. miR-106b inhibitor treatment decreased the TGF-beta 1-stimulated migration of HeLa and SiHa cells. DAB2, a predicted target gene of miR-106b, was inhibited by TGF-beta 1 partly through miR-106b and was involved in TGF-beta 1-induced cervical cancer cell migration. The expression of DAB2 was low in cervical cancer tissues, and negatively correlated with miR-106b expression. Finally, DAB2 was identified as a miR-106b-directed target gene by dual-luciferase reporter assay. Conclusion: Our data suggest that the TGF-beta 1/miR-106b/DAB2 axis may be involved in the pathogenesis of cervical carcinoma.National Natural Science Foundation of China [81472429, 81471893, 81270157]; National Basic Research Program of China (973 Program) [2013CB933702, 2014CBA02003]SCI(E)PubMedARTICLElizijian@bjmu.edu.cn; gengli1957@bjmu.edu.cn113