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Musashi-2, a novel oncoprotein promoting cervical cancer cell growth and invasion, is negatively regulated by p53-induced miR-143 and miR-107 activation

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Title: Musashi-2, a novel oncoprotein promoting cervical cancer cell growth and invasion, is negatively regulated by p53-induced miR-143 and miR-107 activation
Authors: Dong, Peixin Browse this author →KAKEN DB
Xiong, Ying Browse this author
Hanley, Sharon J. B. Browse this author →KAKEN DB
Yue, Junming Browse this author
Watari, Hidemichi Browse this author →KAKEN DB
Keywords: Musashi-2
C-FOS
p53
microRNA-143
microRNA-107
Mithramycin a
Anti-tumor antibiotic
Cervical cancer
Metastasis
Issue Date: 26-Oct-2017
Publisher: BioMed Central
Journal Title: Journal of Experimental & Clinical Cancer Research
Volume: 36
Start Page: 150
Publisher DOI: 10.1186/s13046-017-0617-y
Abstract: Background: Although previous studies have shown promise for targeting Musashi RNA-binding protein 2 (MSI-2) in diverse tumors, the role and mechanism of MSI-2 for cervical cancer (CC) progression and the regulation of MSI-2 expression remains unclear. Methods: Using gene expression and bioinformatic analysis, together with gain- and loss-of-function assays, we identified MSI-2 as a novel oncogenic driver and a poor prognostic marker in CC. We explored the regulation of c-FOS by MSI-2 via RNA-immunoprecipitation and luciferase assay, and confirmed a direct inhibition of MSI-2 by miR-143/miR-107 using luciferase assay. We assessed the effect of a natural antibiotic Mithramycin A on p53, miR-143/miR-107 and MSI-2 expression in CC cells. Results: MSI-2 mRNA is highly expressed in CC tissues and its overexpression correlates with lower overall survival. MSI-2 promotes CC cell growth, invasiveness and sphere formation through directly binding to c-FOS mRNA and by increasing c-FOS protein expression. Furthermore, miR-143/miR-107 are two tumor suppressor miRNAs that directly bind and inhibit MSI-2 expression in CC cells, and downregulation of miR-143/miR-107 associates with poor patient prognosis. Importantly, we found that p53 decreases the expression of MSI-2 through elevating miR-143/miR-107 levels, and treatment with a natural antibiotic Mithramycin A increased p53 and miR-143/miR-107 expression and reduced MSI-2 expression, resulting in the inhibition of CC cell proliferation, invasion and sphere formation. Conclusions: These results suggest that MSI-2 plays a crucial role in promoting the aggressive phenotypes of CC cells, and restoration of miR-143/miR-107 by Mithramycin A via activation of p53 may represent a novel therapeutic approach for CC.
Rights: http://creativecommons.org/licenses/by/4.0/
Type: article
URI: http://hdl.handle.net/2115/67396
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 董 培新

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