title: H3K27 acetylation activated-long non-coding RNA CCAT1 affects cell proliferation and migration by regulating SPRY4 and HOXB13 expression in esophageal squamous cell carcinoma.
abstract: Recently, long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in human cancer biology. In our study, we found that lncRNA CCAT1, whose expression is significantly increased and is correlated with outcomes in Esophageal Squamous Cell Carcinoma (ESCC). Consecutive experiments confirmed that H3K27-acetylation could activate expression of colon cancer associated transcript-1 (CCAT1). Further experiments revealed that CCAT1 knockdown significantly repressed the proliferation and migration both in vitro and in vivo. RNA-seq analysis revealed that CCAT1 knockdown preferentially affected genes that are linked to cell proliferation, cell migration and cell adhesion. Mechanistic investigations found that CCAT1 could serve as a scaffold for two distinct epigenetic modification complexes (5΄ domain of CCAT1 binding Polycomb Repressive Complex 2 (PRC2) while 3΄ domain of CCAT1 binding SUV39H1) and modulate the histone methylation of promoter of SPRY4 (sprouty RTK signaling antagonist 4) in nucleus. In cytoplasm, CCAT1 regulates HOXB13 as a molecular decoy for miR-7, a microRNA that targets both CCAT1 and HOXB13, thus facilitating cell growth and migration. Together, our data demonstrated the important roles of CCAT1 in ESCC oncogenesis and might serve as targets for ESCC diagnosis and therapy.
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: Erbao
authors.initials: E
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Xuzhou Central Hospital, Affiliated Xuzhou Hospital, College of Medicine, Southeast University, Xuzhou, Jiangsu, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Han
authors.affiliation: Central laboratory, Second Affiliated Hospital of Southeast University, Nanjing, Jiangsu, PR China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Yin
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: Xuezhi
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: Linzhi
authors.initials: L
authors.lastname: Hong
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Si
authors.affiliation: Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Baiziting 42, Nanjing 210009, China.
authors.forename: Mantang
authors.initials: M
authors.lastname: Qiu
authors.affiliation: Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: Tongpeng
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: De
authors.affiliation: Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Baiziting 42, Nanjing 210009, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: Yongqian
authors.initials: Y
authors.lastname: Shu
authors.affiliation: Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China.|Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, PR China.|Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: Jinfei
authors.initials: J
authors.lastname: Chen
mesh_terms: D000107:Acetylation; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006657:Histones / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008780:Methyltransferases / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000378:metabolism* / Q000502:physiology; D012097:Repressor Proteins / Q000378:metabolism
chemical_list: D000071221:Enhancer of Zeste Homolog 2 Protein; D006657:Histones; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008780:Methyltransferases; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D062085:RNA, Long Noncoding; D012097:Repressor Proteins; C579842:CCAT1 long noncoding RNA, human; C484414:HOXB13 protein, human; C549242:MIRN7-1 microRNA, human; C499038:SPRY4 protein, human; C407843:SUV39H1 protein, human; C498409:EZH2 protein, human