Long noncoding RNA HOTAIR promotes metastasis of renal cell carcinoma by up-regulating histone H3K27 demethylase JMJD3

Abstract

// Ming Xia 1, 2, 5, * , Lv Yao 4, * , Qiaoxia Zhang 2 , Feng Wang 1 , Hongbin Mei 1 , Xiaoqiang Guo 1, 2, 3, * , Weiren Huang 1, 2 1 Department of Urology, Shenzhen Second People’s Hospital, The First Affliated Hospital of Shenzhen University, Shenzhen 518035, Guangdong, China 2 State Engineering Laboratory of Medical Key Technologies Application of Synthetic Biology, Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People’s Hospital, The First Affliated Hospital of Shenzhen University, Shenzhen 518035, Guangdong, China 3 Laboratory of Molecular Iron Metabolism, College of Life Science, Hebei Normal University, Shijiazhuang 050024, Hebei, China 4 Department of Urology, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU–HKUST Medical Center, Shenzhen, 518036, Guangdong, China 5 Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510000, Guangdong, China * These authors have contributed equally to this work Correspondence to: Weiren Huang, email: pony8980@163.com Xiaoqiang Guo, email: xiaoqiangguo123@163.com Keywords: long noncoding RNA, HOTAIR, renal cell carcinoma, histone demethylase, JMJD3 Received: September 09, 2016     Accepted: January 07, 2017     Published: February 03, 2017 ABSTRACT Long Noncoding RNAs (lncRNAs) are a kind of non-protein coding transcripts longer than 200 nucleotides, and play important roles in diverse biological processes, such as embryonic development and apoptosis. Homeobox (HOX) transcript antisense intergenic RNA (HOTAIR) is a negative prognostic factor in a variety of human cancers, such as breast, liver and lung cancers. HOTAIR can promote cancer cell metastasis by reprogramming chromatin organization. In the present study, HOTAIR expression was elevated in tissues of renal cell carcinoma compared to adjacent normal tissues, and positively correlated with metastasis (P<0.05). The cell migration was inhibited in scratch test and transwell assay after HOTAIR knockdown (P<0.05). Further researches revealed that histone demethylase JMJD3 was reduced and its target gene Snai1 expression was down-regulated after HOTAIR suppression (P<0.05). Meanwhile, the level of histone methytransferase EZH2 target gene PCDHB5 was increased (P<0.05). Collectively, these data suggest that HOTAIR is an important promoter in metastasis of renal cell carcinoma and also plays a dual regulatory role in chromatin state by effecting both histone metylation and demethylation at different gene loci.