title: A comprehensive search for microRNAs with expression profiles modulated by oncogenic KRAS: potential involvement of miR-31 in lung carcinogenesis.
abstract: Small non-protein coding RNAs that regulate messenger RNA levels, namely microRNAs (miRNAs), have been implicated in the pathogenesis of various diseases. The purpose of the present study was to identify essential miRNAs involved in lung carcinogenesis. Previous studies demonstrated that an investigation into the downstream targets of oncogenic KRAS could be used as a strategy to elucidate the molecular mechanisms involved in lung cancer; therefore, we examined the expression profiles of mRNAs modulated by oncogenic KRAS in the present study. We focused on miR-31 from the miRNAs that were differentially expressed, and evaluated its potential role in the development of lung cancer. miR-31 was upregulated not only by oncogenic KRAS, but also by oncogenic EGFR. The expression of miR-31 was markedly attenuated in some lung cancer cell lines by deleting its host gene locus. The restoration of miR-31 in lung cancer cell lines that lost its expression attenuated their growth activities. The knockdown of miR-31 expression in lung cancer cell lines retaining its expression enhanced anchorage-independent growth activity. These results suggest that miR-31 may be a suppressor that regulates an essential oncogenic pathway, the loss of which may promote lung carcinogenesis.
authors: Department of Pathology, Yokohama City University, Graduate School of Medicine, Kanazawa-Ku, Yokohama 236-0004, Japan.
authors: Koji
authors: K
authors: Okudela
authors: Department of Pathology, Yokohama City University, Graduate School of Medicine, Kanazawa-Ku, Yokohama 236-0004, Japan.
authors: Takeshisa
authors: T
authors: Suzuki
authors: Department of Pathology, Yokohama City University, Graduate School of Medicine, Kanazawa-Ku, Yokohama 236-0004, Japan.
authors: Shigeaki
authors: S
authors: Umeda
authors: Department of Pathology, Yokohama City University, Graduate School of Medicine, Kanazawa-Ku, Yokohama 236-0004, Japan.
authors: Yoko
authors: Y
authors: Tateishi
authors: Department of Pathology, Yokohama City University, Graduate School of Medicine, Kanazawa-Ku, Yokohama 236-0004, Japan.
authors: Hideaki
authors: H
authors: Mitsui
authors: Clinical Research Institute, Kanagawa Prefectural Cancer Center Hospital, Asahi-ku, Yokohama 241-8515, Japan.
authors: Yohei
authors: Y
authors: Miyagi
authors: Department of Pathology, Yokohama City University, Graduate School of Medicine, Kanazawa-Ku, Yokohama 236-0004, Japan.
authors: Kenichi
authors: K
authors: Ohashi
mesh_terms: D063646:Carcinogenesis / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D002460:Cell Line; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras); D055752:Small Cell Lung Carcinoma / Q000235:genetics*; D015854:Up-Regulation; D018631:ras Proteins / Q000378:metabolism*
chemical_list: C117307:KRAS protein, human; C534612:MIRN31 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins