title: YY1 regulates melanoma tumorigenesis through a miR-9 ~ RYBP axis.
abstract: BACKGROUND
  The Yin Yang 1 (YY1) transcription factor has been identified to target a plethora of potential target genes, which are important for cell proliferation and differentiation. Although the role that YY1 plays in different human types of cancer has been reported, its biological and mechanistic significance in melanoma has not been well defined.
  
  
  METHODS
  Quantitative RT-PCR analysis was used to determine whether aberrant YY1 and miR-9 expression occurred in melanoma, compared with benign nevi and normal tissue controls. Furthermore, the transcriptional regulation of YY1 on miR-9 expression was assessed by using quantitative ChIP-PCR assay. Subsequently, the effects of YY1 and miR-9 on proliferation, cell cycle, migration and invasion of melanoma cells were detected using CCK-8, flow cytometric analysis, wound healing and transwell invasion assays, respectively. Finally, the post-transcriptional regulation of miR-9 on RYBP was analyzed using luciferase reporter and immunoblot analysis.
  
  
  RESULTS
  Elevated YY1 levels were observed in patients with melanoma, compared with benign nevi and normal tissue controls, and the increased YY1 was associated with melanoma metastasis state and tumor stage. Furthermore, YY1 negatively regulated miR-9 transcription. Silencing of YY1 inhibited proliferation, cell cycle progression, migration and invasion in melanoma cells, while ectopic of miR-9 did the same. Additionally, RYBP was shown to be a direct target of miR-9 through binding to its 3' UTR, thus forming a YY1 ~ miR-9 ~ RYBP axis.
  
  
  CONCLUSIONS
  These results identify a novel YY1 ~ miR-9 ~ RYBP axis involved in melanoma tumorigenesis and reinforce the idea that regulatory circuitries involving miRNAs and TFs are prevalent mechanisms.
authors.affiliation: Department of Dermatology, The Central Hospital of Zibo City, Zibo, 255036, Shandong Province, China. dr_guoweizhao@126.com.
authors.forename: Guowei
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Oncology Department, The Foruth People's Hospital of Zibo City, Zibo, 255067, Shandong Province, China. qiangli_zibo@126.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Dermatology, The Central Hospital of Zibo City, Zibo, 255036, Shandong Province, China. aiqinwang_zibo@126.com.
authors.forename: Aiqin
authors.initials: A
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Qilu Hospital Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong Province, China. jiaojian@medmail.com.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Jiao
mesh_terms: D063646:Carcinogenesis; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins; D014162:Transfection; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; C434957:RYBP protein, human; D012097:Repressor Proteins; D050986:YY1 Transcription Factor; C494698:YY1 protein, human