Sis, 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 PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26509685 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. Keywords: YY1, Melanoma tumorigenesis, miR-9 RYBP axisIntroduction Yin Yang 1 (YY1), also known as , NF-E1, UCRBP and CF1, is a ubiquitously distributed transcription factor belonging to the GLI-Kruppel class of zinc finger proteins that is involved in repressing and activating a diverse number of promoters. Studies have demonstrated the association and modulation of YY1 by the adenovirusderived E1A, an oncoprotein that induces YY1-mediated activation of transcription. In the absence of E1A, the activity of YY1 is reversed, converting to a transcriptional repressor, hence the name Yin Yang 1 [1?]. Since YY1 is a general transcription factor involved in approximately 10 of the total mammalian genes, the expression levels of YY1 must be tightly monitored for the* Correspondence: [email protected] 3 Department of Dermatology, Qilu Hospital Shandong University, 107 Wenhuaxi Road, Jinan 250012, Shandong Province, China Full list of author information is available at the end of the articlesurvival of cells and organisms. Accordingly, abnormal YY1 protein levels have been shown to affect the clinical behavior of several purchase Stattic cancer types [4?]. The putative role of YY1 in tumorigenesis has been supported by its interaction with different molecules. Cicatiello et al. reported that cyclin D1 gene promoter activation in estrogen-responsive human breast cancer is marked by release of the YY1 transcriptional repressor complex including HDAC-1 [10]. Alternatively, YY1 has also been shown to activate c-myc promoter in tumor cells [11, 12]. Moreover, YY1 has been found to be associated with the tumor suppressor p53 [13, 14]. Sui et al. demonstrated that ablation of endogenous YY1 results in p53 accumulation due to a reduction in p53 ubiquitination in vivo [15]. Recent study has revealed that YY1 could help Polycomb Group (PcG) protein recruitment?2015 Zhao et. al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Zhao et al. Journal of Experimental Clinical Cancer Research (2015)34:Page 2 ofto DNA, a novel mechanism by which YY1 used to regulate tumorigenesis [16, 17]. Studies have repeatedly showed that in the majority of th.
