title: Long non-coding RNA ANRIL is upregulated in hepatocellular carcinoma and regulates cell proliferation by epigenetic silencing of KLF2.
abstract: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death, especially in China. And the mechanism of its progression remains poorly understood. Growing evidence indicates that long non-coding RNAs (lncRNAs) are found to be dysregulated in many cancers, including HCC. CDKN2B antisense RNA1 (ANRIL), a lncRNA, coclustered mainly with p14/ARF has been reported to be dysregulated in gastric cancer, esophageal squamous cell carcinoma, and lung cancer. However, its clinical significance and potential role in HCC is still not documented.
  
  
  
  In this study, expression of ANRIL was analyzed in 77 HCC tissues and matched normal tissues by using quantitative real-time polymerase chain reaction (qRT-PCR). ANRIL expression was up-regulated in HCC tissues, and the higher expression of ANRIL was significantly correlated with tumor size and Barcelona Clinic Liver Cancer (BCLC) stage. Moreover, taking advantage of loss of function experiments in HCC cells, we found that knockdown of ANRIL expression could impair cell proliferation and invasion and induce cell apoptosis both in vitro and in vivo. We also found that ANRIL could epigenetically repress KLF2 transcription in HCC cells by binding with PRC2 and recruiting it to KLF2 promoter region. We also found that Sp1 could regulate the expression of ANRIL.
  
  
  
  Our results suggest that lncRNA ANRIL, as a growth regulator, may serve as a new biomarker and target for therapy in HCC.
authors.affiliation: Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an City, Jiangsu Province, 223301, People's Republic of China.
authors.forename: Ming-de
authors.initials: MD
authors.lastname: Huang
authors.affiliation: Department of Oncology, Jining No.1 People's Hospital, No.6, Jiankang Road, Jining City, Shandong Province, 272011, People's Republic of China.
authors.forename: Wen-Ming
authors.initials: WM
authors.lastname: Chen
authors.affiliation: Department of Hepatopancreatobiliary Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an City, Jiangsu Province, 223300, People's Republic of China.
authors.forename: Fu-Zhen
authors.initials: FZ
authors.lastname: Qi
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing City, Jiangsu Province, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Xia
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing City, Jiangsu Province, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing City, Jiangsu Province, People's Republic of China.
authors.forename: Tong-Peng
authors.initials: TP
authors.lastname: Xu
authors.affiliation: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing City, Jiangsu Province, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Yin
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing City, Jiangsu Province, People's Republic of China.
authors.forename: Er-Bao
authors.initials: EB
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing City, Jiangsu Province, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: De
authors.affiliation: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing City, Jiangsu Province, People's Republic of China. yongqian_shu@163.com.
authors.forename: Yong-Qian
authors.initials: YQ
authors.lastname: Shu
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D020868:Gene Silencing; D056945:Hep G2 Cells; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D062085:RNA, Long Noncoding / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection; D015854:Up-Regulation
chemical_list: C561518:CDKN2B antisense RNA, human; C096161:KLF2 protein, human; D051741:Kruppel-Like Transcription Factors; D062085:RNA, Long Noncoding
keywords: ANRIL; HCC; KLF2; Long non-coding RNA; Proliferation