MicroRNA-1251-5p Promotes Carcinogenesis and Autophagy via Targeting the Tumor Suppressor TBCC in Ovarian Cancer Cells

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Accounting for more than 70% of ovarian cancer cases, epithelial ovarian malignancy has a low 5-year survival rate. MicroRNAs may be targeted in the clinical treatment of the disease. In this study, we first found that miR-1251-5p was significantly upregulated in human ovarian cancer cell lines and tissues with the cancer progression and stages. Overexpression or inhibition of miR-1251-5p promoted or impeded cell proliferation and cell cycle progression. Subsequently, TBCC, one of the tubulin-binding cofactors (TBCs), was identified as a target of miR-1251-5p to be negatively associated with cell cycle and autophagy. Exogenous overexpression of TBCC inhibited the expressions of CDK4 and LC3BII, but it promoted the expressions of α/β-tubulin and p62 to suppress cell growth and autophagy, particularly under the starving condition; whereas the introduction of miR-1251-5p in TBCC-overexpressing cells rescued the suppressive effects of TBCC on cell cycle and autophagy through the inverse regulation of the above proteins. Finally, miR-1251-5p was proven to enhance xenograft tumor growth through the downregulation of TBCC but upregulation of Ki67 and LC3B in xenograft tumor tissues. Collectively, these results suggest that miR-1251-5p functions as an oncogene to suppress TBCC and α/β-tubulin expression. Thus, the miR-1251-5p/TBCC/α/β-tubulin axis may be targeted for ovarian cancer treatment. This study demonstrated that miR-1251-5p was upregulated in ovarian cancer (OC) cell lines and closely related to OC recurrence and stages. Overexpression of miR-1251-5p promoted cell proliferation and cell cycle progression in OC cells. TBCC was proven to be a direct target of miR-1251-5p. Upregulation or downregulation of TBCC repressed or promoted cell proliferation, cell cycle progression, and autophagy, whereas miR-1251-5p inversely regulated these effects. miR-1251-5p could also drive tumor growth in vivo. Thus, our findings suggest that the miR-1251-5p/TBCC/α/β-tubulin axis may function as an oncogenic pathway to promote cell cycle and autophagy through the dysregulation of microtubular formation and folding.




Shao, Y., Liu, X., Meng, J., Zhang, X., Ma, Z., & Yang, G. (2019). MicroRNA-1251-5p Promotes Carcinogenesis and Autophagy via Targeting the Tumor Suppressor TBCC in Ovarian Cancer Cells. Molecular Therapy, 27(9), 1653–1664. https://doi.org/10.1016/j.ymthe.2019.06.005

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