title: miR-375 suppresses IGF1R expression and contributes to inhibition of cell progression in laryngeal squamous cell carcinoma.
abstract: MicroRNAs (miRNAs) are small noncoding RNA molecules which are involved in tumorigenesis and development. To investigate their role in primary laryngeal squamous cell carcinoma (LSCC), miRNA GeneChips were used to screen the differentially expressed miRNA, and then validated by real-time quantitative PCR in LSCC samples, we found that miR-375 was frequently downregulated in primary LSCC tissues. The tumor-suppressive effect of miR-375 was determined by in vitro assays; through gain-of-function studies we demonstrated that miR-375 can inhibit LSCC cell (SNU-48 and SNU-899) proliferation, motility, and invasion, and promote their apoptosis. In addition, bioinformatics tools TargetScan, PicTar, and Miranda were used to investigate the potential target of miR-375; bioinformatics analysis and dual-luciferase reporter assay indicated that IGF1R was a novel direct target of miR-375. Ectopic transfection of miR-375 led to a significant reduction in IGF1R and its downstream signaling molecule AKT at both the mRNA and protein levels in LSCC cells. Our results suggested that downregulation of miR-375 is one of the molecular mechanisms for the development and progression of LSCC by directly targeting IGF1R and affecting its downstream AKT signaling pathways. Furthermore, miR-375 and IGF1R may serve as a novel therapeutic target for LSCC.
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Sun Yat-sen University, Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Sun Yat-sen University, Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jianhui
authors.identifier: 0000-0003-4016-183X
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong.
authors.forename: Zenghong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Otorhinolaryngology, The First People's Hospital of Foshan, Foshan, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Qin
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Sun Yat-sen University, Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong.
authors.forename: Thian-Sze
authors.initials: TS
authors.lastname: Wong
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Sun Yat-sen University, Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, China.
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Yang
authors.affiliation: Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, Guangdong 510080, China.
authors.forename: Qing-Ling
authors.initials: QL
authors.lastname: Fu
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Sun Yat-sen University, Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Lei
mesh_terms: D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000096:biosynthesis; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000096:biosynthesis*; D015398:Signal Transduction
chemical_list: C583557:IGF1 protein, human; C000597236:IGF1R protein, human; C540933:MIRN375 microRNA, human; D035683:MicroRNAs; D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D051058:Oncogene Protein v-akt