title: Identification of the NAC1-regulated genes in ovarian cancer.
abstract: Nucleus accumbens-associated protein 1 (NAC1), encoded by the NACC1 gene, is a transcription co-regulator that plays a multifaceted role in promoting tumorigenesis. However, the NAC1-regulated transcriptome has not been comprehensively defined. In this study, we compared the global gene expression profiles of NAC1-overexpressing SKOV3 ovarian cancer cells and NAC1-knockdown SKOV3 cells. We found that NAC1 knockdown was associated with up-regulation of apoptotic genes and down-regulation of genes involved in cell movement, proliferation, Notch signaling, and epithelial-mesenchymal transition. Among NAC1-regulated genes, FOXQ1 was further characterized because it is involved in cell motility and epithelial-mesenchymal transition. NAC1 knockdown decreased FOXQ1 expression and promoter activity. Similarly, inactivation of NAC1 by expression of a dominant-negative construct of NAC1 suppressed FOXQ1 expression. Ectopic expression of NAC1 in NACC1 null cells induced FOXQ1 expression. NAC1 knockdown resulted in decreased cell motility and invasion, whereas constitutive expression of FOXQ1 rescued motility in cells after NAC1 silencing. Moreover, in silico analysis revealed a significant co-up-regulation of NAC1 and FOXQ1 in ovarian carcinoma tissues. On the basis of transcription profiling, we report a group of NAC1-regulated genes that may participate in multiple cancer-related pathways. We further demonstrate that NAC1 is essential and sufficient for activation of FOXQ1 transcription and that the role of NAC1 in cell motility is mediated, at least in part, by FOXQ1.
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland; Sidney Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Ren-Chin
authors.initials: RC
authors.lastname: Wu
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland; Sidney Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Biotechnology Program/Renorbio, Health Science Center, Federal University of Espirito Santo, Vitória, Brazil.
authors.forename: Alice L
authors.initials: AL
authors.lastname: Herlinger
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland; Sidney Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Kailee
authors.initials: K
authors.lastname: Yap
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland; Sidney Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Jung-Won
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Sidney Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Biotechnology Program/Renorbio, Health Science Center, Federal University of Espirito Santo, Vitória, Brazil.
authors.forename: Tian-Li
authors.initials: TL
authors.lastname: Wang
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland; Sidney Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, Maryland. Electronic address: ishih@jhmi.edu.
authors.forename: Ie-Ming
authors.initials: IeM
authors.lastname: Shih
mesh_terms: D015153:Blotting, Western; D002465:Cell Movement / Q000235:genetics; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome; D014162:Transfection
chemical_list: C484579:FOXQ1 protein, human; D051858:Forkhead Transcription Factors; C516477:NACC1 protein, human; D009363:Neoplasm Proteins; D012097:Repressor Proteins