Here we clearly showed for the first time that miR-27a might mediate cell proliferation by regulation of cyclin D1 and p21. Cyclin D1 might play important roles in facilitating the transition from G1 phase into S. The results of luciferase reporter assay suggested that miR-27a might be a transcriptional find more regulator of the cyclin D1 gene. The results of MTT assay indicated that down-regulation of miR-27a promoted drug sensitivity of gastric cancer cells. ADR was then used as probe to evaluate drug accumulation and retention in cancer cells. The results of FCM showed that down-regulation of miR-27a increased ADR accumulation and retention and decreased ADR releasing index, indicating that miR-27a had a direct or indirect
selleck compound function of pumping drug out of cells. The results of real-time PCR and western blot showed that miR-27a might mediate the expression of P-gp, which might function as an ATP-dependent drug-efflux pump. Conclusions In conclusion, down-regulation of miR-27a might inhibit proliferation and drug resistance of gastric cancer cells through regulation of P-gp, cyclin D1 and p21. MiR-27a might be considered as a valuable target for cancer therapy. Acknowledgements This study was supported
in part by grants from the National Scientific Foundation of China (30770635). References 1. Bhardwaj A, Singh S, Singh AP: MicroRNA-based Cancer Therapeutics: Big Hope from Small RNAs. Mol Cell Pharmacol 2010,2(5):213–219.PubMed 2. Kurokawa R: Long noncoding RNA as a regulator for transcription. Prog Mol Subcell Biol 2011, 51:29–41.PubMedCrossRef 3. Zhang H, Li M, Han Y, Hong L, Gong T, Sun L, Zheng X: Down-regulation of miR-27a might reverse multidrug resistance of esophageal squamous cell carcinoma. Dig Dis Sci 2010,55(9):2545–51.PubMedCrossRef
4. Nishi H, Ono K, Horie T, Nagao K, Kinoshita M, Kuwabara Y, Watanabe S, Kimura T: MicroRNA-27a regulates beta cardiac myosin heavy chain gene expression by targeting thyroid hormone receptor beta1 in neonatal rat ventricular myocytes. Mol Cell Biol 2011,31(4):744–55.PubMedCrossRef Adenosine 5. Ma Y, Yu S, Zhao W, Lu Z, Chen J: miR-27a regulates the growth, colony formation and migration of pancreatic cancer cells by targeting Sprouty2. Cancer Lett 2010,298(2):150–8.PubMedCrossRef 6. Allen DL, Loh AS: Posttranscriptional mechanisms involving microRNA-27a and b contribute to fast-specific and glucocorticoid-mediated myostatin expression in skeletal muscle. Am J Physiol Cell Physiol 2011,300(1):124–37.CrossRef 7. Sun Q, Gu H, Zeng Y, Xia Y, Wang Y, Jing Y, Yang L, Wang B: Hsa-mir-27ª genetic ��-Nicotinamide cell line variant contributes to gastric cancer susceptibility through affecting miR-27a and target gene expression. Cancer Sci 2010,101(10):2241–7.PubMedCrossRef 8. Li ZM, Hu S, Xiao L, Wang J, Cai J, Yu LL, Wang ZH: Expression of microRNA 27a and its correlation with drug resistance in human ovarian cancer A2780/Taxol cells. Zhonghua Fu Chan Ke Za Zhi 2010,45(5):372–5.PubMed 9.