title: MicroRNA-200 promotes lung cancer cell growth through FOG2-independent AKT activation.
abstract: MicroRNA-200 (miR-200) has emerged as a regulator of the PI3K/AKT pathway and cancer cell growth. It was reported that miR-200 can activate PI3K/AKT by targeting FOG2 (friend of GATA 2), which directly binds to the p85α regulatory subunit of PI3K. We found that miR-200 was elevated in early stage lung adenocarcinomas when compared with normal lung tissues, and the expression of miR-200 promoted the tumor spheroid growth of lung adenocarcinoma cells. We show that AKT activation was essential for such oncogenic action of miR-200. However, depletion of FOG2 had little effect on AKT activation. By performing a reverse-phase protein array, we found that miR-200 not only activated AKT but also concomitantly inactivated S6K and increased IRS-1, an S6K substrate that is increased on S6K inactivation. Depletion of IRS-1 partially inhibited the miR-200-dependent AKT activation. Taken together, our results suggest that miR-200 may activate AKT in lung adenocarcinoma cells through a FOG2-independent mechanism involving IRS-1. Our findings also provide evidence that increased miR-200 expression may contribute to early lung tumorigenesis and that AKT inhibitors may be useful for the treatment of miR-200-dependent tumor cell growth.
authors: Thoracic Disease Research Unit, Division of Pulmonary and Critical Care Medicine, Department of Biochemistry and Molecular Biology, Cancer Center and College of Medicine, Mayo Clinic, Rochester, MN, USA.
authors: Lixia
authors: L
authors: Guo
authors: Thoracic Disease Research Unit, Division of Pulmonary and Critical Care Medicine, Department of Biochemistry and Molecular Biology, Cancer Center and College of Medicine, Mayo Clinic, Rochester, MN, USA.
authors: Jingyu
authors: J
authors: Wang
authors: Division of Health Sciences, Cancer Center and College of Medicine, Mayo Clinic, Rochester, MN, USA.
authors: Ping
authors: P
authors: Yang
authors: Division of Health Sciences, Cancer Center and College of Medicine, Mayo Clinic, Rochester, MN, USA.
authors: Qiang
authors: Q
authors: Lu
authors: Thoracic Disease Research Unit, Division of Pulmonary and Critical Care Medicine, Department of Biochemistry and Molecular Biology, Cancer Center and College of Medicine, Mayo Clinic, Rochester, MN, USA.
authors: Ting
authors: T
authors: Zhang
authors: Thoracic Disease Research Unit, Division of Pulmonary and Critical Care Medicine, Department of Biochemistry and Molecular Biology, Cancer Center and College of Medicine, Mayo Clinic, Rochester, MN, USA.
authors: Yanan
authors: Y
authors: Yang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D040081:Protein Array Analysis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D014157:Transcription Factors; C117427:ZFPM2 protein, human; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT; lung cancer; microRNA-200; signaling