PMID- 25184138 OWN - NLM STAT- MEDLINE DCOM- 20150511 LR - 20220409 IS - 2314-6141 (Electronic) IS - 2314-6133 (Print) VI - 2014 DP - 2014 TI - miR-375 suppresses IGF1R expression and contributes to inhibition of cell progression in laryngeal squamous cell carcinoma. PG - 374598 LID - 10.1155/2014/374598 [doi] LID - 374598 AB - 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. FAU - Luo, Jie AU - Luo J AD - Department of Otorhinolaryngology, The First Affiliated Hospital of Sun Yat-sen University, Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, China. FAU - Wu, Jianhui AU - Wu J AUID- ORCID: 0000-0003-4016-183X AD - Department of Otorhinolaryngology, The First Affiliated Hospital of Sun Yat-sen University, Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, China. FAU - Li, Zenghong AU - Li Z AD - Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong. FAU - Qin, Hao AU - Qin H AD - Department of Otorhinolaryngology, The First People's Hospital of Foshan, Foshan, China. FAU - Wang, Bin AU - Wang B AD - Department of Otorhinolaryngology, The First Affiliated Hospital of Sun Yat-sen University, Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, China. FAU - Wong, Thian-Sze AU - Wong TS AD - Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong. FAU - Yang, Weiqiang AU - Yang W AD - Department of Otorhinolaryngology, The First Affiliated Hospital of Sun Yat-sen University, Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, China. FAU - Fu, Qing-Ling AU - Fu QL AD - Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, Guangdong 510080, China. FAU - Lei, Wenbin AU - Lei W AD - Department of Otorhinolaryngology, The First Affiliated Hospital of Sun Yat-sen University, Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140812 PL - United States TA - Biomed Res Int JT - BioMed research international JID - 101600173 RN - 0 (IGF1 protein, human) RN - 0 (IGF1R protein, human) RN - 0 (MIRN375 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Receptors, Somatomedin) RN - 67763-96-6 (Insulin-Like Growth Factor I) RN - EC 2.7.10.1 (Receptor, IGF Type 1) RN - EC 2.7.11.1 (Oncogene Protein v-akt) SB - IM MH - Apoptosis MH - Carcinoma, Squamous Cell/*genetics/pathology MH - Cell Line, Tumor MH - Cell Proliferation/genetics MH - Cell Transformation, Neoplastic/genetics MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Insulin-Like Growth Factor I/*biosynthesis/genetics MH - Laryngeal Neoplasms/*genetics/pathology MH - MicroRNAs/*genetics/metabolism MH - Oncogene Protein v-akt/biosynthesis MH - Receptor, IGF Type 1 MH - Receptors, Somatomedin/*biosynthesis MH - Signal Transduction PMC - PMC4145380 EDAT- 2014/09/04 06:00 MHDA- 2015/05/12 06:00 PMCR- 2014/08/12 CRDT- 2014/09/04 06:00 PHST- 2014/03/16 00:00 [received] PHST- 2014/06/17 00:00 [revised] PHST- 2014/06/24 00:00 [accepted] PHST- 2014/09/04 06:00 [entrez] PHST- 2014/09/04 06:00 [pubmed] PHST- 2015/05/12 06:00 [medline] PHST- 2014/08/12 00:00 [pmc-release] AID - 10.1155/2014/374598 [doi] PST - ppublish SO - Biomed Res Int. 2014;2014:374598. doi: 10.1155/2014/374598. Epub 2014 Aug 12.