长链非编码RNA肺腺癌转移相关转录本1及其在肿瘤转移中的作用

Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1and its effect in cancer metastasis

肺腺癌转移相关转录本1(MALAT1)是一种长度约8 000 nt的长链非编码RNA(lncRNA),其在3'端构成"三螺旋"结构,保护自身免遭降解,在功能上一定程度取代了多聚腺苷酸[poly(A)]。MALAT1的表达受到TAR DNA结合蛋白43(TDP-43)、DiGeorge综合征危象区基因8蛋白(DGCR8)及后垂体激素等多个不同层面的调控。MALAT1介导包括丝氨酸/精氨酸(SR)蛋白向具有转录活性的基因位点聚集,从而控制选择性剪切;也可导致生长基因改变核内位置,有效激活转录单元。此外,癌细胞中MALAT1呈高水平表达,并与Wnt/β-连环蛋白信号通路、Bcl-2家族等密切关联,是癌细胞侵袭和转移的重要因素。同时,MALAT1通过MYB相关蛋白B(B-MYB)和异质核糖核蛋白C(hnRNP C)影响细胞周期和有丝分裂,造成癌细胞增殖。lncRNA无论作为癌症诊断和预后标志物,还是新型治疗靶点,都将为癌症的诊断和治疗带来新的突破口。

The metastasis-associated lung adenocarcinoma transcript 1 （MALAT1） is a long non-coding RNA （lncRNA） with a length of about 8000 nt. The 3＇ end of MALAT1 is protected from degradation by an evolutionarily conserved triple helix and its function can partly replace poly （ A）. The expression of MALAT1 is regulated by TDP-43, DGCR8, and posterior pituitary hormone oxytocin, etc. MALAT1 influences the recruitment of SR proteins to transcription sites and controls the alternative splicing. MALAT1 causes the relocation of growth control genes and effectively activates the transcription unit. Besides, MALAT1 expresses highly in cancer ceils and closely associates with the Wnt/b-catenin signaling pathway and Bcl-2 family. It is a key factor of cancer invasion and metastasis. Meanwhile, MALAT1 mediates B-MYB and hnRNP C, influences the cell cycle and mitosis, and causes the proliferation of cancer cells. As the diagnostic marker, prognostic marker, or new therapeutic target, lncRNA is helpful for the therapy and diagnosis of cancers.