Long non-coding RNA ANRIL is upregulated in hepatocellular carcinoma and regulates cell apoptosis by epigenetic silencing of KLF2

Journal of Hematology & Oncology

Yong-qian Shu⁵  Wei De²  Er-bao Zhang²  Li Yin⁵  Tong-peng Xu⁵  Ming Sun²  Rui Xia²  Fu-zhen Qi⁴  Wen-ming Chen³  Ming-de Huang¹ 

[1] Department of Medical Oncology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an City 223301, Jiangsu Province, People’s Republic of China;Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing City, Jiangsu Province, People’s Republic of China;Department of Oncology, Jining No. 1 People’s Hospital, No. 6, Jiankang Road, Jining City 272011, Shandong Province, People’s Republic of China;Department of Hepatopancreatobiliary Surgery, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an City 223300, Jiangsu Province, People’s Republic of China;Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing City, Jiangsu Province, People’s Republic of China

关键词: KLF2;    Proliferation;    HCC;    ANRIL;    Long non-coding RNA;   

Others  :  1217425
DOI  :  10.1186/s13045-015-0146-0

 received in 2015-01-16, accepted in 2015-04-29,  发布年份 2015

【 摘 要 】

Background

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. ANRIL, a lncRNA co-clustered 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 are 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 polymerase chain reaction (qRT-PCR). ANRIL expression was upregulated 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 Kruppel-like factor 2 (KLF2) transcription in HCC cells by binding with PRC2 and recruiting it to the 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.

【 授权许可】

   
2015 Huang et al.; licensee BioMed Central.

【 图 表 】

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