title: Suppression of MicroRNA-7 (miR-7) Biogenesis by Nuclear Factor 90-Nuclear Factor 45 Complex (NF90-NF45) Controls Cell Proliferation in Hepatocellular Carcinoma.
abstract: MicroRNA-7 (miR-7)has been characterized as an anti-oncogenic microRNA (miRNA) in several cancers, including hepatocellular carcinoma (HCC). However, the mechanism for the regulation of miR-7 production in tumors remains unclear. Here, we identified nuclear factor 90 (NF90) and NF45 complex (NF90-NF45) as negative regulators of miR-7 processing in HCC. Expression of NF90 and NF45 was significantly elevated in primary HCC tissues compared with adjacent non-tumor tissues. To examine which miRNAs are controlled by NF90-NF45, we performed an miRNA microarray and quantitative RT-PCR analyses of HCC cell lines. Depletion of NF90 resulted in elevated levels of mature miR-7, whereas the expression of primary miR-7-1 (pri-miR-7-1) was decreased in cells following knockdown of NF90. Conversely, the levels of mature miR-7 were reduced in cells overexpressing NF90 and NF45, although pri-miR-7-1 was accumulated in the same cells. Furthermore, NF90-NF45 was found to bind pri-miR-7-1 in vitro These results suggest that NF90-NF45 inhibits the pri-miR-7-1 processing step through the binding of NF90-NF45 to pri-miR-7-1. We also found that levels of the EGF receptor, an oncogenic factor that is a direct target of miR-7, and phosphorylation of AKT were significantly decreased in HCC cell lines depleted of NF90 or NF45. Of note, knockdown of NF90 or NF45 caused a reduction in the proliferation rate of HCC cells. Taken together, NF90-NF45 stimulates an elevation of EGF receptor levels via the suppression of miR-7 biogenesis, resulting in the promotion of cell proliferation in HCC.
authors: From the Laboratory of Molecular Biology, Science Research Center.
authors: Takuma
authors: T
authors: Higuchi
authors: From the Laboratory of Molecular Biology, Science Research Center.
authors: Hiroshi
authors: H
authors: Todaka
authors: From the Laboratory of Molecular Biology, Science Research Center.
authors: Yasunori
authors: Y
authors: Sugiyama
authors: Departments of Gastroenterology and Hepatology and.
authors: Masafumi
authors: M
authors: Ono
authors: the Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors: Nobuyuki
authors: N
authors: Tamaki
authors: the Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors: Etsuro
authors: E
authors: Hatano
authors: Surgery, and.
authors: Yuka
authors: Y
authors: Takezaki
authors: Surgery, and.
authors: Kazuhiro
authors: K
authors: Hanazaki
authors: From the Laboratory of Molecular Biology, Science Research Center.
authors: Takeshi
authors: T
authors: Miwa
authors: From the Laboratory of Molecular Biology, Science Research Center.
authors: Sylvia
authors: S
authors: Lai
authors: From the Laboratory of Molecular Biology, Science Research Center.
authors: Keiko
authors: K
authors: Morisawa
authors: Division of Laboratory Animal Science, Science Research Center,Kochi Medical School, Kochi 783-8505 and.
authors: Masayuki
authors: M
authors: Tsuda
authors: From the Laboratory of Molecular Biology, Science Research Center.
authors: Taketoshi
authors: T
authors: Taniguchi
authors: From the Laboratory of Molecular Biology, Science Research Center, sshuji@kochi-u.ac.jp.
authors: Shuji
authors: S
authors: Sakamoto
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D051903:Nuclear Factor 45 Protein / Q000235:genetics / Q000378:metabolism*; D050779:Nuclear Factor 90 Proteins / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D046912:Multiprotein Complexes; D009363:Neoplasm Proteins; D051903:Nuclear Factor 45 Protein; D050779:Nuclear Factor 90 Proteins; D012334:RNA, Neoplasm; C494013:ILF2 protein, human; C429643:ILF3 protein, human; C549242:MIRN7-1 microRNA, human
keywords: RNA-binding protein; epidermal growth factor receptor (EGFR); hepatocellular carcinoma; microRNA (miRNA); microRNA biogenesis