title: miR-491-5p suppresses cell growth and invasion by targeting Notch3 in nasopharyngeal carcinoma.
abstract: MicroRNAs (miRNAs) have critical roles in the progression of nasopharyngeal carcinoma (NPC), a highly invasive and metastatic cancer that is widely prevalent in Southern China. miR-491-5p has been implicated in multiple types of cancer; however, its biological role and underlying mechanism in NPC have not been fully explored. In the present study, we found that miR-491-5p was downregulated in NPC tissues and cell lines compared with the corresponding normal counterparts. Overexpression of miR-491-5p significantly inhibited cell proliferation, migration and invasion in vitro and suppressed tumor growth in vivo. Using miRNA target prediction algorithms and reporter assays, we showed that miR-491-5p suppressed Notch3 expression both at the mRNA and protein level through directly targeting the 3' untranslated region (3'-UTR) of Notch3 mRNA. Overexpression of Notch3 significantly reversed the tumor-suppressive effects of miR‑491-5p. Taken together, the present study reveals a mechanistic link between miR-491-5p and Notch3 in the pathogenesis of NPC and that miR-491-5p has potential as a therapeutic target for NPC.
authors.affiliation: Department of ENT, Jinshan Hospital Affiliated to Fudan University, Shanghai 201508, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of ENT, Jinshan Hospital Affiliated to Fudan University, Shanghai 201508, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of ENT, Jinshan Hospital Affiliated to Fudan University, Shanghai 201508, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of ENT, Jinshan Hospital Affiliated to Fudan University, Shanghai 201508, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of ENT, Jinshan Hospital Affiliated to Fudan University, Shanghai 201508, P.R. China.
authors.forename: Lin-Gen
authors.initials: LG
authors.lastname: Xu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D002277:Carcinoma; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D000071656:Receptor, Notch3 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C551410:MIRN491 microRNA, human; D035683:MicroRNAs; C499374:NOTCH3 protein, human; D012333:RNA, Messenger; D000071656:Receptor, Notch3