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10.1074/jbc.M116.748210

http://scihub22266oqcxt.onion/10.1074/jbc.M116.748210
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suck abstract from ncbi


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pmid27519414
      J+Biol+Chem 2016 ; 291 (40 ): 21074-21084
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  • Suppression of MicroRNA-7 (miR-7) Biogenesis by Nuclear Factor 90-Nuclear Factor 45 Complex (NF90-NF45) Controls Cell Proliferation in Hepatocellular Carcinoma #MMPMID27519414
  • Higuchi T ; Todaka H ; Sugiyama Y ; Ono M ; Tamaki N ; Hatano E ; Takezaki Y ; Hanazaki K ; Miwa T ; Lai S ; Morisawa K ; Tsuda M ; Taniguchi T ; Sakamoto S
  • J Biol Chem 2016[Sep]; 291 (40 ): 21074-21084 PMID27519414 show ga
  • 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.
  • |*Cell Proliferation [MESH]
  • |Adult [MESH]
  • |Carcinoma, Hepatocellular/genetics/*metabolism [MESH]
  • |Female [MESH]
  • |Humans [MESH]
  • |Liver Neoplasms/genetics/*metabolism [MESH]
  • |Male [MESH]
  • |MicroRNAs/genetics/*metabolism [MESH]
  • |Middle Aged [MESH]
  • |Multiprotein Complexes/genetics/*metabolism [MESH]
  • |Neoplasm Proteins/genetics/*metabolism [MESH]
  • |Nuclear Factor 45 Protein/genetics/*metabolism [MESH]
  • |Nuclear Factor 90 Proteins/genetics/*metabolism [MESH]


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