MicroRNA-218 inhibits bladder cancer cell proliferation, migration, and invasion by targeting BMI-1
MicroRNAs (miRNAs) are recognized as important molecules and have emerged as important gene regulators in tumorigenesis. Growing evidence suggested that miR-218 was a tumor suppressor in many human cancers. However, its underlying role in bladder cancer (BCa) remains unclear. The aim of this study was to explore the effect of miR-218 on the proliferation, migration, and invasion of BCa cells. We found that miR-218 was frequently downregulated in BCa tissues compared with normal adjacent tissues. In vitro and in vivo assays demonstrated that miR-218 overexpression in the BCa cells inhibited cell proliferation, migration, and invasion. Luciferase reporter assay showed that BMI-1 was a direct target of miR-218. In addition, we found that miR-218 regulated the expression of BMI-1 and its downstream target (PTEN) and participated in the phosphorylation of AKT. Our findings indicate that miR-218 functions as tumor suppressor in BCa, and the miR-218/BMI-1 axis may provide novel diagnostic and therapeutic strategies for the treatment of BCa.
KeywordsMicroRNA-218 Bladder cancer BMI-1 Proliferation Migration Invasion
- 20.Kang MK, Kim RH, Kim SJ, Yip FK, Shin KH, Dimri GP, et al. Elevated Bmi-1 expression is associated with dysplastic cell transformation during oral carcinogenesis and is required for cancer cell replication and survival. Br J Cancer. 2007;96(1):126–33. doi:10.1038/sj.bjc.6603529.CrossRefPubMedGoogle Scholar
- 21.Song LB, Li J, Liao WT, Feng Y, Yu CP, Hu LJ, et al. The polycomb group protein Bmi-1 represses the tumor suppressor PTEN and induces epithelial-mesenchymal transition in human nasopharyngeal epithelial cells. J Clin Invest. 2009;119(12):3626–36. doi:10.1172/JCI39374.CrossRefPubMedPubMedCentralGoogle Scholar
- 25.Gong Y, Wang X, Liu J, Shi L, Yin B, Peng X, et al. NSPc1, a mainly nuclear localized protein of novel PcG family members, has a transcription repression activity related to its PKC phosphorylation site at S183. FEBS Lett. 2005;579(1):115–21. doi:10.1016/j.febslet.2004.11.056.CrossRefPubMedGoogle Scholar
- 27.Xu Z, Liu H, Lv X, Liu Y, Li S, Li H. Knockdown of the Bmi-1 oncogene inhibits cell proliferation and induces cell apoptosis and is involved in the decrease of Akt phosphorylation in the human breast carcinoma cell line MCF-7. Oncol Rep. 2011;25(2):409–18. doi:10.3892/or.2010.1078.PubMedGoogle Scholar
- 28.Li X, Yang Z, Song W, Zhou L, Li Q, Tao K, et al. Overexpression of Bmi-1 contributes to the invasion and metastasis of hepatocellular carcinoma by increasing the expression of matrix metalloproteinase (MMP)2, MMP-9 and vascular endothelial growth factor via the PTEN/PI3K/Akt pathway. Int J Oncol. 2013;43(3):793–802. doi:10.3892/ijo.2013.1992.PubMedGoogle Scholar