title: miR-3941: A novel microRNA that controls IGBP1 expression and is associated with malignant progression of lung adenocarcinoma.
abstract: Immunoglobulin (CD79a) binding protein 1 (IGBP1) is universally overexpressed in lung adenocarcinoma and exerts an anti-apoptotic effect by binding to PP2Ac. However, the molecular mechanism of IGBP1 overexpression is still unclear. In the present study, we used a microRNA (miRNA) array and TargetScan Human software to detect IGBP1-related miRNAs that regulate IGBP1 expression. The miRNA array analysis revealed more than 100 miRNAs that are dysregulated in early invasive adenocarcinoma. On the other hand, in silico analysis using TargetScan Human revealed 79 miRNAs that are associated with IGBP1 protein expression. Among the miRNAs selected by miRNA array analysis, six (miR-34b, miR-138, miR-374a, miR-374b, miR-1909, miR-3941) were also included among those selected by TargetScan analysis. Real-time reverse transcription PCR (real-time RT-PCR) showed that the six microRNAs were downregulated in invasive adenocarcinoma (IGBP1+) relative to adjacent normal lung tissue (IGBP1-). Among these microRNAs, only miR-34b and miR-3941 depressed luciferase activity by targeting 3'UTR-IGBP1 in the luciferase vector. We transfected miR-34b and miR-3941 into lung adenocarcinoma cell lines (A549, PC-9), and both of them suppressed IGBP1 expression and cell proliferation. Moreover, the transfected miR-34b and miR-3941 induced apoptosis of a lung adenocarcinoma cell line, similarly to the effect of siIGBP1 RNA. As well as miR-34b, we found that miR-3941 targeted IGBP1 specifically and was able to exclusively downregulate IGBP1 expression. These findings indicate that suppression of miR-3941 has an important role in the progression of lung adenocarcinoma at an early stage.
authors.affiliation: Department of Pathology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba-shi, Ibaraki, Japan.
authors.forename: Taiki
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Shiba-Ishii
authors.affiliation: Department of Pathology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba-shi, Ibaraki, Japan.
authors.forename: Yunjung
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Pathology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba-shi, Ibaraki, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Dai
authors.affiliation: Department of Pathology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba-shi, Ibaraki, Japan.
authors.forename: Ryan Edbert
authors.initials: RE
authors.lastname: Husni
authors.affiliation: Department of Pathology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba-shi, Ibaraki, Japan.
authors.forename: JeongMin
authors.initials: J
authors.lastname: Hong
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Kano
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Sakashita
authors.affiliation: Department of Pathology, Ibaraki Prefectural Central Hospital, Kasama-shi, Ibaraki, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Iijima
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Noguchi
mesh_terms: D000072283:A549 Cells; D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics*; D018832:Molecular Chaperones; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C490467:IGBP1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C522425:MIRN34 microRNA, human; C000617891:MIRN3941 microRNA, human; D035683:MicroRNAs; D018832:Molecular Chaperones
keywords: Carcinogenesis; IGBP1; lung adenocarcinoma; miR-34b; miR-3941