Xia Ming, Yao Lv, Zhang Qiaoxia, Wang Feng, Mei Hongbin, Guo Xiaoqiang, Huang Weiren
Department of Urology, Shenzhen Second People's Hospital, The First Affliated Hospital of Shenzhen University, Shenzhen 518035, Guangdong, China.
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.
Oncotarget. 2017 Mar 21;8(12):19795-19802. doi: 10.18632/oncotarget.15047.
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.
长链非编码RNA（lncRNAs）是一类长度超过200个核苷酸的非蛋白质编码转录本，在多种生物学过程中发挥重要作用，如胚胎发育和细胞凋亡。同源框（HOX）转录本反义基因间RNA（HOTAIR）是多种人类癌症（如乳腺癌、肝癌和肺癌）中的负性预后因子。HOTAIR可通过重编程染色质组织促进癌细胞转移。在本研究中，与相邻正常组织相比，肾细胞癌组织中HOTAIR表达升高，且与转移呈正相关（P<0.05）。HOTAIR敲低后，划痕试验和Transwell试验中的细胞迁移受到抑制（P<0.05）。进一步研究表明，HOTAIR抑制后，组蛋白去甲基化酶JMJD3减少，其靶基因Snai1表达下调（P<0.05）。同时，组蛋白甲基转移酶EZH2靶基因PCDHB5的水平升高（P<0.05）。总体而言，这些数据表明HOTAIR是肾细胞癌转移的重要促进因子，并且通过影响不同基因位点的组蛋白甲基化和去甲基化在染色质状态中发挥双重调节作用。
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