Abstract
Cervical cancer is one of the most frequent gynecological malignancies in women worldwide. MicroRNA-195 (miR-195) was recently found highly expressed in cervical cancer. However, the role of miR-195 in the pathology of cervical cancer remains poorly understood. In this study, we first confirmed the downregulation of miR-195 in primary cervical cancer tissues. For the functional study, we introduced the sequences of miR-195 or miR-195 inhibitor into Hela and SiHa cervical cancer cell lines. Overexpression of miR-195 inhibited the proliferation of both Hela and SiHa cells. In contrast, reducing the endogenous miR-195 level by miR-195 inhibitor promoted the proliferation of cervical cancer cells. Flow cytometric assay showed that overexpression of miR-195 induced G1 phase arrest, whereas miR-195 inhibitor shortened G1 phase of cervical cancer cells. In addition, the suppressive role of miR-195 in cell cycle was also demonstrated by the western blot results of various cell cycle indicators, such as phosphorylated retinoblastoma (p-Rb) and proliferating cell nuclear antigen (PCNA), in the gain and loss of function experiments. Furthermore, Dual-Luciferase Reporter Assay revealed that miR-195 targeted the 3′-untranslated region of cyclin D1a transcript, such as to regulate cyclin D1 expression. In summary, our results suggest that miR-195 acts as a suppressor in the proliferation and cell cycle of cervical cancer cells by directly targeting cyclin D1a mRNA.
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Acknowledgments
This study was supported by grants from the National Nature Science Foundation of China (No. 81202047), the Program for Liaoning Excellent Talents in University (No. LJQ2013083), the Higher Specialized Research Fund for the Doctoral Program (No. 20122104110014), and the Free Researcher Project of Shengjing Hospital (No. 201302).
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Wang, N., Wei, H., Yin, D. et al. MicroRNA-195 inhibits proliferation of cervical cancer cells by targeting cyclin D1a. Tumor Biol. 37, 4711–4720 (2016). https://doi.org/10.1007/s13277-015-4292-3
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DOI: https://doi.org/10.1007/s13277-015-4292-3