snoRNA来源的pi-sno81对乳腺癌中FOXO3a表达的影响

Influence of snoRNA-derived pi-sno81 on FOXO3a expression in breast cancer

目的探讨snoRNA来源的piRNA在乳腺癌中对FOXO3a基因的影响。方法将5个化学合成的pi-snoRNAs(pi-sno44/74/75/78/81)分别转入MDA-MB-231乳腺癌细胞后收样提取总RNA,检测每个piRNA对FOXO3a m RNA水平的影响,找出对FOXO3a作用最明显的piRNA,验证其对FOXO3a蛋白水平的影响;收集2016年3月~2016年10月在我科行乳腺根治手术的乳腺癌患者术后新鲜肿瘤及瘤旁标本28对,检测其中pi-sno81、sno81及FOXO3a的表达情况;应用典型相关分析对pi-sno81、sno81及FOXO3a在乳腺癌及癌旁乳腺组织中的表达情况进行相关性分析,了解pi-sno81与FOXO3a的相关性。结果 qRT-PCR检测发现,FOXO3a基因表达被pisno44/74/75/81上调;其中pi-sno81上调FOXO3a最明显,且pi-sno81明显上调了FOXO3a蛋白水平;FOXO3a在乳腺癌中呈低表达;相关性分析发现,pi-sno81在乳腺癌及癌旁乳腺组织中的表达与FOXO3a在乳腺癌及癌旁乳腺组织中的表达成正相关(P<0.001,Corr=0.835)。结论 snoRNA来源的pi-sno81能上调乳腺癌细胞中FOXO3a基因的表达,并可能通过影响FOXO3a的表达影响乳腺癌细胞的生长。

Objective To investigate the influence of snoRNA-derived piRNA on FOXO3a gene in breast cancer.Methods Five chemically synthesized pi-snoRNAs including pi-sno44,pi-sno74,pi-sno75,pi-sno78,and pi-sno81 were trans-leered into MDA-MB-231 breast cancer cells and the total RNA was extracted.EachpiRNA was detected in order to find its influence on FOXO3a mRNA levels as well as the most effective piRNA on FOXO3a,and then testified its in- fluence on FOXO3a level.The fresh tumor and peritumoral specimen in 28 pairs in breast cancer patients undergone the radical surgery of the mammary gland in our department from March to October in 2016 were collected.Among them, expressions of pi-sno81,sno81,and FOXO3a were detected.Expressions of pi-snoSl,sno81,and FOXO3a in breast cancer and adjacent mammary gland tissue were in correlation analysis aiming at understanding the correlation of pi-snoSland FOXO3a by canonical correlation analysis.Results qRT-PCR detected the expression of FOXO3a was up-regulated by pi-sno44,pi-sno74,pi-sno75,and pi-sno81,of which pi-sno81 was in most remarkable on up-regulating FOXO3a.Be- sides,pi-sno81 greatly up-regulated the protein level of FOXO3a,a low expression in breast cancer.Correlation analysis detected that expression of pi-sno81 in breast cancer and adjacent mammary gland tissue was in positive correlation with FOXO3a in expression of breast cancer and adjacent mammary gland tissue （P〈0.001,Corr=0.835）.Conclusion The snoRNA-derived pi-sno81 can up-regulate the expression of FOXO3a gene in breast cancer cells,and may affect the growth of breast cancer cells by influencing FOXO3a expression.