长链非编码RNA H19在缺氧环境中的作用机制研究进展

Research progress of long chain non-coding RNA H19 in anoxic environment mechanism

H19印记基因编码的长链非编码RNA H19在细胞内发挥重要的调控作用。在缺氧细胞中,H19基因表达发生变化,其涉及的转录因子以及蛋白表达相应发生变化。在特异性蛋白1的参与下,低氧诱导因子-1α(hypoxiainducible factor-1α,HIF-1α)直接与H19启动子结合,诱导缺氧条件下H19表达上调。在缺氧情况下,肿瘤抑制蛋白p53也可能通过干扰HIF-1α活性来介导H19基因的表达。H19外显子1编码的miR675-5p,通过促进细胞核内HIF-1α的积累和降低HIF-1α的生物抑制剂VHL基因表达来促进缺氧反应。另外,缺氧条件下细胞膜表面转运蛋白表达发生变化,细胞内糖代谢途径从有氧氧化向无氧糖酵解的转变也与H19的参与有关。H19可能是维持缺氧条件下细胞内代谢平衡,促进细胞在缺氧条件下进行适应性生存的一个关键基因。

LncRNA H19 encoded by the H19 imprinting gene plays an important regulatory role in the cell. Recently study has found that in hypoxic cells, the expression of H19 gene changes, and the transcription factors and protein involved in the expression change accordingly. Through the involvement of specific protein 1 （SP1）, hypoxia-inducible factor-1α （HIF-1α） binds directly to the H19 promoter and induces the up-regulation of H19 expression under hypoxic conditions. The tumor suppressor protein p53 may also mediate the expression of the H19 gene, in part by interfering with HIF-la activity under hypoxia stress. The miR675-5p encoded by exon 1 of H19 promotes hypoxia response by driving the nuclear accumulation of HIF-1α and reducing the expression of VHL gene, which is a physiological HIF-1α inhibitor. In addition, under the condition of hypoxia, the expression of transporter on cell membrane changes, and the transition of the intracellular glucose metabolism pathway from aerobic oxidation to anaerobic glycolysis is also involved in the involvement of H19. Therefore, H19 may be a key gene that maintains intracellular balance under hypoxic conditions and drives adaptive cell survival under conditions of hypoxia stress.