长链非编码RNA LINC01355在神经母细胞瘤复发过程中的表达变化及意义

Expression and significance of long non-coding RNA LINC01355 during recurrence of neuroblastoma

目的探讨神经母细胞瘤(NB)复发过程中长链非编码RNA(lncRNA)LINC01355的表达及作用机制。方法在TARGET数据库检索NB数据集,进行差异表达分析筛选差异表达的lncRNA并进行生物信息学分析。荧光实时定量反转录-聚合酶链反应(RT-qPCR)法检测20例原发NB组织及10例复发NB组织中部分差异分子的表达,对数据库结果进行验证,组间比较采用t检验。结果LINC01355在复发NB组织中表达水平(1.935±1.242)明显低于原发肿瘤组织(6.800±5.107,Z=3.395,P<0.01)。将患者按LINC01355表达的中位数分为两个亚组,并使用Kaplan-Meier方法估算这两个亚组的总生存时间,结果表明,LINC01355高表达对应患者预后情况较好(χ2=6.002,P<0.05)。应用Starbase 3.0数据库分析LINC01355的靶基因及功能,GO富集分析结果显示LINC01355调控的靶基因参与了自噬调节、神经元凋亡过程、类固醇生物合成等过程;京都基因与基因组百科全书(KEGG)分析显示LINC01355及其靶基因参与了乏氧诱导因子-1α(HIF-1α)通路的调控。对LINC01355及其靶基因法尼基二磷酸法尼基转移酶1(FDFT1)mRNA在原发及复发NB组织中表达进行验证,结果发现复发NB组织中LINC01355表达(0.926±0.223)低于原发肿瘤(2.695±1.036,t=-5.294,P<0.01);复发NB组织中FDFT1 mRNA表达(3.989±1.996)高于原发肿瘤(1.505±0.680,t=5.079,P<0.01);在原发及复发NB组织中LINC01355与FDFT1 mRNA表达呈负相关(rs=-0.826、-0.900,P<0.01)。结论LINC01355可用于预测NB患者的预后,与肿瘤复发有关。LINC01355的表达降低导致FDFT1表达增高可能是NB复发的重要原因。

Objective To investigate the expression and mechanism of long non-coding RNA(lncRNA)LINC01355 in recurrence of neuroblastoma(NB).Methods The data of NB were retrieved from the TARGET database,and differential expression analysis was performed to screen out differentially expressed lncRNAs and bioinformatics analysis was done.The expression of some differential molecules in 20 primary NB tissues and 10 recurrent NB tissues was detected by fluorescent real-time quantitative reverse transcription-polymerase chain reaction(RT-qPCR).Results Results of difference analysis showed that the expression level of LINC01355 in recurrent NB tissue(1.935±1.242)was significantly lower than that in primary tumor tissue(6.800±5.107,Z=3.395,P<0.01).The results of survival analysis showed that the patients were divided into two subgroups according to the median expression of LINC01355,and the Kaplan-Meier analysis was employed to estimate the overall survival time of the two subgroups.The results showed that high expression of LINC01355 corresponded to better prognosis of patients(χ^(2)=6.002,P<0.05).The Starbase3.0 database was used to analyze the target genes and functions of LINC01355.The results of GO enrichment analysis showed that the target genes regulated by LINC01355 were involved in autophagy regulation,neuronal apoptosis,and steroid biosynthesis.Kyoto encyclopedia of genes and genomes(KEGG)analysis showed that LINC01355 and its target genes were involved in the regulation of hypoxia-inducible factor-1α(HIF-1α)pathway.The expression of LINC01355 and farnesyl diphosphate farnesyltransferase 1(FDFT1)mRNA in primary and recurrent NB tissues was verified.The results showed that the expression of LINC01355 in the recurrent NB tissue(0.926±0.223)was lower than that in the primary tumor(2.695±1.036,t=-5.294,P<0.01),which was consistent with the results of bioinformatics.The expression of FDFT1 mRNA in the recurrent NB tissue(3.989±1.996)was higher than that in the primary tumor(1.505±0.680,t=5.079,P<0.01),and negatively correlations were confirmed between LINC01355 and FDFT1 mRNA in primary and recurrent NB tissues(rs=-0.826,-0.900,P<0.01).Conclusion LINC01355 could be used to predict the prognosis of NB patients,and was associated with tumor recurrence.The down-regulation of LINC01355 led to the up-regulation of FDFT1,which might be an important factor for the recurrence of NB.