长链非编码RNA,HOTAIR在肿瘤中的研究进展

[摘要] 长链非编码RNA（lncRNAs）在人类基因组普遍被转录且起着重要的调控作用。这类多聚腺苷酸RNA长度大于200 nt，不编码任何蛋白质，但与肿瘤的发生发展及转移预后密切相关。HOX 转录反义RNA（HOX transcript antisense RNA，HOTAIR）全长2158个碱基，首次被发现以反式转录作用调控基因的表达。HOTAIR作为组蛋白修饰复合物的支架，5’端结构域结合多梳抑制复合体2（PRC2），3’端结构域结合组蛋白去甲基化酶复合体[赖氨酸特异性组蛋白去甲基化酶1（LSD1）/RE1-沉默转录因子（REST）共阻抑蛋白（CoREST）/REST]，并介导这两种复合体至特定基因位点，分别使染色体组蛋白H3第27位赖氨酸三甲基化（H3K27me3）和组蛋白H3第4位赖氨酸去二甲基化（H3K4me2），从而使长达40 kb的碱基发生表观遗传学沉默。最近临床研究表明：HOTAIR表达水平与多种肿瘤（如乳腺癌、结直肠癌、肝癌、胰腺癌、喉癌等）的发生发展及转移预后密切相关。高表达HOTAIR能抑制抑癌基因的表达，促进肿瘤复发转移，而下调HOTAIR表达则降低肿瘤细胞的转移侵袭能力。尽管众多研究表明HOTAIR与肿瘤的发生发展有密切关系，但其具体作用机制还有待进一步探究。

[关键词] 长链非编码RNA；HOTAIR；肿瘤

[中图分类号] R73 [文献标识码] A [文章编号] 2095-0616（2013）13-28-05

Research progress of long non-coding RNA HOTAIR in the human cancers

CAO Linping WU Jian ZHENG Shusen

Department of Hepatobiliary Surgery， First Affiliated Hospital， School of Medicine， Zhejiang University， Key Laboratory of Combined Multi-organ Transplantation of Ministry of Public Health， Hangzhou 310003， China

[Abstract] Long non-coding RNAs （lncRNAs） are pervasively transcribed and vital regulators in the human genome. These long， polyadenylated RNAs which defined as RNA>200 nucleotides in length are lack of protein-coding functions， while they demonstrate potential roles both in oncogenic and tumor suppressive pathways. HOX transcript antisense RNA （HOTAIR）， a 2158 nucleotide， spliced， was first found to have regulatory functions of reverse transcription. It may serve as a scaffold for at least two histone modification complexes. The 5" domain of HOTAIR binding Polycomb Repressive Complex 2 （PRC2） and the 3" domain binding the histone demethylase complex [LSD1 （lysine specific demethylase 1）/CoREST （Co-repressor of RE1-silencing transcription factor）/REST] can target the two complexes to the specific gene sites， resulting in histone H3 tri-methylated at lysine 27 （H3K27me3） and histone H3 dimethyl Lys4 （H3K4me2）. These lead to silence 40 kilobases of genes. Recently， clinical studies have shown a positive correlation among high expression levels of HOTAIR， subsequent metastasis， death and recurrence of many cancers， such as breast cancer， colorectal cancer， liver cancer， pancreatic cancer， laryngeal squamous cell carcinoma et al. The over-expression of HOTAIR can inhibit the expression of cancer-related suppressor genes and improve the malignant ability of tumors； contrary， down-regulation of HOTAIR can decrease the metastatic capability of many cancer cells. Although the relationship between HOTAIR and cancer has been studied， the underlying molecular mechanisms are still unclear. The function of HOTAIR related to cancer represents a major mission that should be carried out in the near future.