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: Yong Peng, Yuntao Dai, Charles Hitchcock, Xiaojuan Yang, Edmund S Kassis, Lunxu Liu, Zhenghua Luo, Hui-Lung Sun, Ri Cui, Huijun Wei, Taewan Kim, Tae Jin Lee, Young-Jun Jeon, Gerard J Nuovo, Stefano Volinia, Qianchuan He, Jianhua Yu, Patrick Nana-Sinkam, Carlo M Croce
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 110 Issue 37 Pg. 15043-8 (Sep 10 2013) ISSN: 1091-6490 [Electronic] United States
• PMID: 23980150 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• 3' Untranslated Regions
• IGF1 protein, human
• MIRN486 microRNA, human
• MicroRNAs
• Phosphoinositide-3 Kinase Inhibitors
• RNA, Small Interfering
• Insulin-Like Growth Factor I
• Class Ia Phosphatidylinositol 3-Kinase
• Receptor, IGF Type 1

Topics

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