Abstract
MicroRNAs are important regulators of multiple cellular processes, and aberrant miRNA expression has been observed in human cervical cancer (CC). The present study was to evaluate the level of miR-195 and cyclin D1 in CC tissues and cells. We further investigated the molecular mechanisms of miR-195 and cyclin D1 in CC cell lines HeLa and SiHa. Here, we found that miR-195 expression was down-regulated in CC tissues, and HeLa and SiHa cells (all p < 0.001). By contrast, cyclin D1 was up-regulated. Furthermore, the expression of miR-195 was inversely proportional to that of cyclin D1 mRNA or protein (p = 0.013, p = 0.015, respectively). In vitro studies demonstrated that the overexpression of miR-195 played a suppressor role in the proliferation of HeLa and SiHa cells and promoted cell apoptosis. Luciferase reporter assays confirmed that miR-195 binding to the 3′-UTR regions of cyclin D1 inhibited the expression of cyclin D1 in HeLa and SiHa cells. However, the inhibitor of miR-195 promoted the expression of cyclin D1 and cell proliferation. In conclusion, our data suggest that miR-195 may have the potential role in treatment of CC patients, as well as miR-195 is a novel regulator of invasiveness and tumorigenicity in CC cells by targeting cyclin D1. MiR-195/cyclin D1 pathway may be a useful therapeutic agent in CC patients.
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Acknowledgments
This study is supported by General Program of National Natural Science Foundation of China (No. 81272866) and National Natural Science Funds for Distinguished Young Scholars (No. 81302274). We thank all the patients who were willing to be recruited in this investigation.
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Zhen Li and Hua Wang contributed equally to this work as the co-first author.
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Li, Z., Wang, H., Wang, Z. et al. MiR-195 inhibits the proliferation of human cervical cancer cells by directly targeting cyclin D1. Tumor Biol. 37, 6457–6463 (2016). https://doi.org/10.1007/s13277-015-4540-6
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DOI: https://doi.org/10.1007/s13277-015-4540-6