Insulin growth factor signaling is regulated by microRNA-486, an underexpressed microRNA in lung cancer.

Peng Y, Dai Y, Hitchcock C, Yang X, Kassis ES, Liu L, Luo Z, Sun HL, Cui R, Wei H, Kim T, Lee TJ, Jeon YJ, Nuovo GJ, Volinia S, He Q, Yu J, Nana-Sinkam P, Croce CM
Proc Natl Acad Sci U S A. 2013 110 (37): 15043-8

PMID: 23980150 · PMCID: PMC3773758 · DOI:10.1073/pnas.1307107110

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.

MeSH Terms (22)

3' Untranslated Regions Animals Apoptosis Carcinoma, Non-Small-Cell Lung Cell Cycle Checkpoints Cell Line, Tumor Cell Movement Cell Proliferation Class Ia Phosphatidylinositol 3-Kinase Gene Expression Regulation, Neoplastic Genes, p53 Genes, Tumor Suppressor Humans Insulin-Like Growth Factor I Lung Neoplasms Mice Mice, Nude MicroRNAs Phosphoinositide-3 Kinase Inhibitors Receptor, IGF Type 1 RNA, Small Interfering Signal Transduction

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