Msi1 promotes tumor growth and cell proliferation by targeting cell cycle checkpoint proteins p21, p27 and p53 in cervical carcinomas
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Xian Liu1, Wen-Ting Yang1, Peng-Sheng Zheng1,2
1 Department of Reproductive Medicine, The First Affiliated Hospital of the Medical College, Xi’an Jiaotong University, Xi’an, The People’s Republic of China
2 Section of Cancer Stem Cell Research, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of the People’s Republic of China, Xi’an, The People’s Republic of China
Peng-Sheng Zheng, e-mail: [email protected]
Keywords: Msi1, cervical cancer, cell cycle, oncogene
Received: July 06, 2014 Accepted: September 28, 2014 Published: October 24, 2014
Musashi RNA-binding protein1 (Msi1), a member of the RNA-binding protein family, has been reported to be a diagnostic marker and potential therapeutic target in some cancers, its function in cervical cancer remains unknown. In this study, we found Msi1 was highly expressed in cervical cancer tissues, and over-expressing Msi1 in cervical cancer cells enhanced tumor formation and cell proliferation and accelerated cells into the S phase. Whereas, down-regulating Msi1 by shRNA in cervical cancer cells inhibited tumor formation and cell proliferation and slowed cell into the S phase, suggesting that Msi1 might act as cell cycle regulator. Immunohistochemistry assay showed the negative correlation between Msi1 and p21, p27 and p53, suggesting that Msi1 might regulate these cycle regulators in cervical cancer. Moreover, the expression of the p21, p27 and p53 proteins were down-regulated in Msi1 overexpressing cervical cancer cells and up-regulated in shMsi1 cervical cancer cells. Luciferase assays and RNA-protein binding assays confirmed that Msi1 could bind to the mRNA 3’UTRs of p21, p27 and p53 and suppress the translation of these proteins. Our findings provide new evidence that Msi1 might promote cell proliferation by accelerating the cell cycle by directly targeting p21, p27 and p53.
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