长链非编码RNA HOTAIR的信号通路、作用机制及与消化系统肿瘤的关系

Signal pathway and mechanism of long non-coding RNA HOTAIR and its relationship with digestive system tumors

长链非编码RNA(LncRNA)广泛参与机体生理和病理过程。其中,HOX转录反义RNA(HOTAIR)由HOXC基因座的反义链转录,却主要调控HOXD基因。HOTAIR能引导多梳抑制复合体2(PRC2)和赖氨酸特异性组蛋白去甲基化酶1(LSD1)复合体靶向特定目标基因,使组蛋白H3第27位赖氨酸三甲基化(H3K27me3)和组蛋白H3第4位赖氨酸二甲基化(H3K4me2),引起染色体状态重编程,从而使染色体封闭,继而导致靶基因沉默。HOTAIR与人类多种肿瘤如肝细胞癌、胰腺癌、胃肠道间质瘤和大肠癌等的发生、发展、复发以及转移有着相关性,有望成为相关肿瘤的预测指标和新的治疗靶点。该文阐述了HOTAIR的可能作用机制及其信号通路,并总结了其与上述各类肿瘤关系研究的最新进展。

Long non-coding RNAs （LncRNA） widely involve in physical and pathological processes of human body. Among them, the HOX transcript antisense RNA （HOTAIR） is transcribed by HOXC gene but mainly regulates the HOXD gene. The HOTAIR can mediate the polycomb repressive complex 2 （PRC2） and histone demethylase complex [ LSD1 （ lysine specific demethylase 1）/CoREST （Co-repressor of REl-silencing transcription factor） /REST] to their target genes, and leads to histone H3 tri-methylated at lysine27 （H3K27rne3） and histone H3 dimethylated at Lysine4 （ H3K4me2）. This causes chromosome state reprogramming and chromosome closing, and consequently resulting in target gene silencing. HOTAIR is relevant to the oncogenesis, progression, recurrence and metastasis of various human cancers, such as hepatocellular carcinoma, pancreatic cancer, gastrointestinal stromal tumors, and colorectal cancer. It is a potential prediction index and new therapeutic target for related cancers. This paper discusses possible molecular mechanisms and signal pathways of HOTAIR and summarizes the latest research developments of the relationship between HOTA1R and forementioned cancers.