title: Insulin growth factor signaling is regulated by microRNA-486, an underexpressed microRNA in lung cancer.
abstract: MicroRNAs (miRNAs) are small 19- to 24-nt noncoding RNAs that have the capacity to regulate fundamental biological processes essential for cancer initiation and progression. In cancer, miRNAs may function as oncogenes or tumor suppressors. Here, we conducted global profiling for miRNAs in a cohort of stage 1 nonsmall cell lung cancers (n = 81) and determined that miR-486 was the most down-regulated miRNA in tumors compared with adjacent uninvolved lung tissues, suggesting that miR-486 loss may be important in lung cancer development. We report that miR-486 directly targets components of insulin growth factor (IGF) signaling including insulin-like growth factor 1 (IGF1), IGF1 receptor (IGF1R), and phosphoinositide-3-kinase, regulatory subunit 1 (alpha) (PIK3R1, or p85a) and functions as a potent tumor suppressor of lung cancer both in vitro and in vivo. Our findings support the role for miR-486 loss in lung cancer and suggest a potential biological link to p53.
authors: Department of Molecular Virology, Immunology, and Medical Genetics and Division of Hematology, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210.
authors: Yong
authors: Y
authors: Peng
authors: Yuntao
authors: Y
authors: Dai
authors: Charles
authors: C
authors: Hitchcock
authors: Xiaojuan
authors: X
authors: Yang
authors: Edmund S
authors: ES
authors: Kassis
authors: Lunxu
authors: L
authors: Liu
authors: Zhenghua
authors: Z
authors: Luo
authors: Hui-Lung
authors: HL
authors: Sun
authors: Ri
authors: R
authors: Cui
authors: Huijun
authors: H
authors: Wei
authors: Taewan
authors: T
authors: Kim
authors: Tae Jin
authors: TJ
authors: Lee
authors: Young-Jun
authors: YJ
authors: Jeon
authors: Gerard J
authors: GJ
authors: Nuovo
authors: Stefano
authors: S
authors: Volinia
authors: Qianchuan
authors: Q
authors: He
authors: Jianhua
authors: J
authors: Yu
authors: Patrick
authors: P
authors: Nana-Sinkam
authors: Carlo M
authors: CM
authors: Croce
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D034741:RNA, Small Interfering / Q000235:genetics; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D020413:3' Untranslated Regions; C583557:IGF1 protein, human; C560945:MIRN486 microRNA, human; D035683:MicroRNAs; D000081082:Phosphoinositide-3 Kinase Inhibitors; D034741:RNA, Small Interfering; D007334:Insulin-Like Growth Factor I; D058543:Class Ia Phosphatidylinositol 3-Kinase; D017526:Receptor, IGF Type 1
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