丙酮酸激酶前mRNA可变剪接的调控在肿瘤代谢中的作用和意义

Significance of the Regulated Mechanism of Alternative Splicing of Pyruvate Kinase pre-mRNA in Metabolism of Tumor

丙酮酸激酶是糖酵解的关键酶之一,丙酮酸激酶m基因前mRNA(pre-mRNA)通过可变剪接产生M1和M2型两种丙酮酸激酶异构体,2种异构体的选择性表达决定肿瘤细胞的代谢表型,改变肿瘤细胞的增殖和生长。因此,调控丙酮酸激酶可变剪接,对于控制肿瘤细胞的生长代谢十分重要。研究发现,核不均一核糖核蛋白(hnRNP)A1/A2及多聚嘧啶结合蛋白(PTB,又称hnRNPⅠ)具有调控丙酮酸激酶前mRNA可变剪接的作用,并且致癌转录因子c-Myc与hnRNP A1/A2及PTB在肿瘤细胞中的过表达密切相关。我们结合相关研究进展,简要综述丙酮酸激酶可变剪接调控机制。

Pyruvate kinase is one of the key enzymes in glycolysis.Pyruvate kinase M1 and M2 isoform are produced by pre-mRNA alternative splicing of transcripts of the pyruyate kinase m gene（pkm）.Selective expression of M1 and M2 isoform determines the metabolic phenotype of tumor cells,cell proliferation and tumor growth.Thus,regulation of alternative splicing of the pkm gene for control tumor cell growth and metabolism is very important.A recent study showed that the alternative splicing event was controlled by heterogeneous nuclear ribonucleoprotein（hnRNP） family members hnRNP A1 and hnRNP A2,and polypyrimidine tract binding protein（PTB,also known as hnRNPⅠ）.And oncogenic transcription factor c-Myc is related to overexpression of hnRNP A1/A2 and PTB in cancer cell.Based on the results of the previous studies and the latest researches,this review focused on the mechanism of alternative splicing of the pkm gene.