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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  
   
نویسنده dong p. ,xiong y. ,hanley s.j.b. ,yue j. ,watari h.
منبع journal of experimental and clinical cancer research - 2017 - دوره : 36 - شماره : 1
چکیده    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. © 2017 the author(s).
کلیدواژه Anti-tumor antibiotic; C-FOS; Cervical cancer; Metastasis; microRNA-107; microRNA-143; Mithramycin a; Musashi-2; p53
آدرس department of women's health educational system,hokkaido university school of medicine,hokkaido university,sapporo,0608638, Japan, department of gynecology,state key laboratory of oncology in south china,sun yat-sen university cancer center,guangzhou,510060, China, department of women's health educational system,hokkaido university school of medicine,hokkaido university,sapporo,0608638, Japan, department of pathology and laboratory medicine,university of tennessee,health science center,memphis,tn 38163,united states,center for cancer research,university of tennessee,health science center,memphis,tn 38163, United States, department of obstetrics and gynecology,hokkaido university,school of medicine,hokkaido university,sapporo,0608638, Japan
 
     
   
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