Lung cancer. However, its clinical significance and potential role in HCC is still not documented. Methods and results: 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. Conclusion: Our results suggest that lncRNA ANRIL, as a growth regulator, may serve as a new biomarker and target for therapy in HCC. Keywords: Long non-coding RNA, ANRIL, HCC, Proliferation, KLFBackground Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death globally. Half of these deaths were estimated to occur in China . The prognosis of patients with HCC remains poor despite the therapeutic advances in HCC treatment recently. Therefore, a great challenge lies ahead in the understanding of the molecular mechanisms of hepatocarcinogenesis and the identification of the new biomarkers for HCC that will supply an arm for improving diagnosis and management of human HCC.* Correspondence: [email protected] Equal contributors 5 Department of Oncology, First Affiliated Hospital, Doravirine msds Nanjing Medical University, Nanjing City, Jiangsu Province, People’s Republic of China Full PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28192408 list of author information is available at the end of the article?2015 Huang et al.Long non-coding RNAs (LncRNAs) are non-protein coding transcripts with a length greater than 200 nucleotides. Accumulating evidence showed that lncRNAs participated in cancer cells biological processes, such as cell growth, cell metastasis, cell differentiation, and fate decision [2?]. Additionally, many studies demonstrate that lncRNAs play a critical role in tumorigenesis, and their misexpression confers tumor initiation and cancer cell growth and metastasis [5?]. For example, lncRNA HOTAIR is dysregulated in many cancers [8, 9]. Moreover, it could promote the invasion-metastasis cascade in cancer cells by binding to PRC2 . In a word, there has been a heavy focus on the ways that lncRNAs contribute to cancer development. However, their aberrantHuang et al. Journal of Hematology Oncology (2015) 8:Page 2 ofexpression and functional roles in HCC development are still not well-documented. Among them, lncRNA CDKN2B antisense RNA 1 (ANRIL) is transcribed from the INK4b-ARF-INK4a gene cluster in the opposite direction, which has been identified as a genetic susceptibility locus shared associated by coronary disease, intracranial aneurysm, type 2 diabetes, and also cancers [10, 11]. Moreover, ANRIL could be induced by ATM-E2F1 signaling pathway and is required for the silencing of p15INK4B by recruiting PRC2 [12, 13]. In our previous study, we found that ANRIL was overexpressed and played an important role in gastric carcinogenesis and NSCLC development [14, 15]. However, the functional role and underlying mechanism of ANRIL in HCC remains unclear. Here we investigate the relationship between.