IGF2BP2调控食管癌细胞增殖和凋亡相关基因可变剪接的机制研究  

Study on mechanism of IGF2BP2 in regulating alternative splicing of genes related to cell proliferation and apoptosis in esophageal cancer cell

作　　者：冯静芳 唐勇[1] 马兰英[1] 李凡周 韩梅[1] FENG Jingfang;TANG Yong;MA Lanying;LI Fanzhou;HAN Mei(Department of Gastroenterology,Affiliated Cancer Hospital of Xinjiang Medical University,Urumqi,Xinjiang 830011,China)

机构地区：[1]新疆医科大学附属肿瘤医院消化内科,乌鲁木齐830011

出　　处：《重庆医学》2022年第16期2839-2846,共8页Chongqing medicine

基　　金：新疆维吾尔自治区自然科学基金青年基金项目(2018D01C270)。

摘　　要：目的探讨胰岛素样生长因子2 mRNA结合蛋白2(IGF2BP2)通过调控基因表达和可变剪接在食管癌发生、发展中的作用机制。方法在人食管癌细胞系ECA109中对IGF2BP2进行过表达,并进行转录组测序,通过分析IGF2BP2所调控的差异表达基因和可变剪接基因,探讨IGF2BP2在食管癌中的作用机制。结果IGF2BP2过表达后引起158个基因显著差异表达,其中上调基因81个,下调基因77个(FC≥2 or≤0.5,P<0.01),基因本体(GO)、京都基因与基因组百科全书分析发现IGF2BP2通过调控差异表达基因的方式影响食管癌的发生、发展,可能并不显著。IGF2BP2过表达可变剪接水平发生显著变化的基因,在GO分析中富集到糖基磷脂酰肌醇锚定生物合成过程,主要富集的信号通路是细胞增殖和细胞凋亡等。在细胞增殖中具有丰富意义的可变剪接基因发现,IGF2BP2过表达后21个(ADAMTSL4、TRIO、PLEKHG2等)在细胞增殖方面可变剪接的基因。在细胞凋亡中具有丰富意义的可变剪接基因发现了23个(细胞周期蛋白依赖性激酶11B、制瘤素M的细胞因子受体、MRE11A等)在IGF2BP2过表达后调控细胞凋亡的可变剪接基因。结论IGF2BP2调控食管癌基因可变剪接促进其发生和发展。Objective To explore the mechanism of IGF2 BP2 in the occurrence and development of esophageal cancer through regulation of gene expression and alternative splicing.Methods IGF2 BP2 was overexpressed in the human esophageal cancer cell line ECA109,and the transcriptome sequencing was performed.By analyzing the differentially expressed genes and alternatively spliced genes regulated by IGF2 BP2,the mechanism of action of IGF2 BP2 in esophageal cancer was explored.Results Over-expression of IGF2 BP2 caused significantly differential expression of 158 genes,of which 81 genes were up-regulated and 77 genes were down-regulated(FC≥2 or≤0.5,P<0.01).GO and KEGG analysis found that IGF2 BP2 regulating the way of differentially expressing genes to affect the occurrence and development of esophageal cancer might not be significant.IGF2 BP2 over-expressed the genes whose alternative splicing levels having significant change,which enriched in GPI anchors biosynthesis process in GO analysis.The main enriched signal pathways were the cell proliferation and apoptosis.There are abundant alternative splicing genes in cell proliferation.After over-expression of IGF2 BP2,21 genes(ADAMTSL4,TRIO,PLEKHG2,etc.)that were alternatively spliced in cell proliferation were found.For alternative splicing genes with abundant significance in cell apoptosis,23 alternative splicing genes(CDK11 B,OSMR,MRE11 A,etc.)regulating cell apoptosis after over-expression of IGF2 BP2 were discovered.Conclusion IGF2 BP2 regulates alternative splicing of esophageal oncogene and promotes its occurrence and development.

关 键 词：食管癌 IGF2BP2 可变剪接 细胞增殖 细胞凋亡 

分 类 号：R735.1[医药卫生—肿瘤]