title: MicroRNA-95 promotes cell proliferation and targets sorting Nexin 1 in human colorectal carcinoma.
abstract: MicroRNAs (miRNAs) are strongly implicated in cancer but their specific roles and functions in the major cancers have yet to be fully elucidated. In this study, we defined the oncogenic significance and function of miR-95, which we found to be elevated in colorectal cancer (CRC) tissues by microarray analysis. Evaluation of an expanded CRC cohort revealed that miR-95 expression was up-regulated in nearly half of the tumors examined (42/87) compared with the corresponding noncancerous tissues. Ectopic overexpression of miR-95 in human CRC cell lines promoted cell growth in vitro and tumorigenicity in vivo, whereas RNAi-mediated silencing of miR-95 decreased cell growth ratio. Mechanistic studies revealed that miR-95 repressed the expression of reporter gene coupled to the 3'-untranslated region of sorting nexin 1 (SNX1), whereas miR-95 silencing up-regulated SNX1 expression. Moreover, miR-95 expression levels correlated inversely with SNX1 protein levels in human CRC tissues. RNAi-mediated knockdown of SNX1 phenocopied the proliferation-promoting effect of miR-95, whereas overexpression of SNX1 blocked miR-95-induced proliferation of CRC cells. Taken together, these results demonstrated that miR-95 increases proliferation by directly targeting SNX1, defining miR-95 as a new oncogenic miRNA in CRC.
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Huang
authors.forename: Shenglin
authors.initials: S
authors.lastname: Huang
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Wang
authors.forename: Linhui
authors.initials: L
authors.lastname: Liang
authors.forename: Shujuan
authors.initials: S
authors.lastname: Ni
authors.forename: Lisha
authors.initials: L
authors.lastname: Wang
authors.forename: Weiqi
authors.initials: W
authors.lastname: Sheng
authors.forename: Xianghuo
authors.initials: X
authors.lastname: He
authors.forename: Xiang
authors.initials: X
authors.lastname: Du
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D058305:Sorting Nexins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; C575854:MIRN95 microRNA, human; D035683:MicroRNAs; C513978:SNX1 protein, human; D058305:Sorting Nexins