肿瘤转移新靶点HOTAIR的研究进展

Review of a new tumor metastatic target HOTAIR

HOX转录反义RNA(HOX transcript antisenseRNA,HOTAIR)是第一个被发现具有反式转录调控作用的长链非编码RNA(long non-coding RNA,lncRNA),它能同时结合多梳抑制复合体2(polycomb repressive complex2,PRC2)和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(lysine specific demethylase1,LSD1)/RE1-沉默转录因子(RE1-silencing transcription factor,REST)共阻抑蛋白(Co-repressor of REST,CoREST)/REST],并介导这2种复合体结合到特异性的基因组位点,分别使染色体组蛋白H3第27位赖氨酸三甲基化(histone H3 tri-methyl at edatlysine27,H3K27me3)和组蛋白H3第4位赖氨酸二甲基化(histone H3 dimethyl Lys4,H3K4me2),继而导致基因沉默。临床研究表明,乳腺癌、结肠癌和肝癌等肿瘤组织中HOTAIR的表达水平与肿瘤的转移、复发以及预后紧密相关。肿瘤细胞中高表达HOTAIR能够抑制相关肿瘤转移抑制基因的表达,促进肿瘤恶变;反之,沉默HOTAIR的表达可使肿瘤细胞丧失转移能力。

HOX transcript antisense RNA （HOTAIR） is the first long non-coding RNA （lncRNA） which was found to have regulatory functions of reverse transcription. It can simultaneously bind to polycomb repressive complex 2 （PRC2） and histone demethylase complex [LSD1 （lysine specific demethylase 1）/CoREST （Co-repressor of RE1-silencing transcription factor）/REST] and mediates the binding of these two complexes to the specific gene sites, resulting in histone H3 tri-methylated at lysine 27 （H3K27me3） and histone H3 dimethyl Lys4 （H3K4me2）, and ultimately leading to gene silencing. Clinical studies have shown close relationships of the expression of HOTAIR with metastasis and recurrence of many cancers such as breast cancer, colorectal cancer and liver cancer, as well as the prognosis of the patients with these cancers. The high expression level of HOTAIR can inhibit the expression of cancer-related metastasis suppressor genes and improve the malignant transformation of tumors; conversely, HOTAIR silencing can decrease the metastatic capability of cancer cells.