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Hokkaido University Collection of Scholarly and Academic Papers >
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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)
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Submitter: 董 培新
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