オノ　マサフミ   ONO Masafumi   小野　正文    所属   医学部 医学科（附属足立医療センター）    職種   非常勤講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Suppression of MicroRNA-7 (miR-7) Biogenesis by Nuclear Factor 90-Nuclear Factor 45 Complex (NF90-NF45) Controls Cell Proliferation in Hepatocellular Carcinoma.
掲載誌名	正式名：The Journal of biological chemistry 略　 称：J Biol Chem ISSNコード：1083351X/00219258
掲載区分	国外
巻・号・頁	291(40),pp.21074-21084
著者・共著者	Higuchi Takuma, Todaka Hiroshi, Sugiyama Yasunori, Ono Masafumi, Tamaki Nobuyuki, Hatano Etsuro, Takezaki Yuka, Hanazaki Kazuhiro, Miwa Takeshi, Lai Sylvia, Morisawa Keiko, Tsuda Masayuki, Taniguchi Taketoshi, Sakamoto Shuji
発行年月	2016/09
概要	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.
DOI	10.1074/jbc.M116.748210
PMID	27519414