Abstract
We report that elevated microRNA-133b (miR-133b) acts as an oncogene in human cervical carcinoma to promote tumorigenesis and metastasis. In situ hybridization confirmed that miR-133b is localized in proliferating human cervical carcinoma cells with levels progressively elevating throughout advancing stages. Cellular studies showed that miR-133b enhances cell proliferation and colony formation by targeting mammalian sterile 20-like kinase 2 (MST2), cell division control protein 42 homolog (CDC42) and ras homolog gene family member A (RHOA), which subsequently results in activation of the tumorigenic protein kinase B alpha (AKT1) and mitogen-activated protein kinase (ERK1 and ERK2, here abbreviated as ERK) signaling pathways. Mouse experiments revealed that upregulation of miR-133b in cervical carcinoma cells strongly promotes both in vivo tumorigenesis and independent metastasis to the mouse lung. The data indicates that upregulation of miR-133b shortens the latency of cervical carcinoma. Together, these findings suggest that miR-133b could be a potent marker for the early onset of cervical carcinoma.
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Acknowledgements
We thank Drs Youyong Lu and Yun Zhang for discussions and comments on the manuscript; Suqiong Wang, Zhaoli Chen and Dapeng Ding for help with mouse experiments; Jiantao Cui and Dr Bing Dong for help with IHC and ISH experiments. This study was supported by the National High-tech Program of China (grant no. 2006AA020701 and grant no. 2009AA022701).
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Qin, W., Dong, P., Ma, C. et al. MicroRNA-133b is a key promoter of cervical carcinoma development through the activation of the ERK and AKT1 pathways. Oncogene 31, 4067–4075 (2012). https://doi.org/10.1038/onc.2011.561
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DOI: https://doi.org/10.1038/onc.2011.561
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