宫颈癌放化疗前后LncRNA的表达谱变化及意义

Significance of Different Expression Profiles of LncRNA in Cervical Cancer Before and After Radiotherapy and Chemotherapy

目的:研究宫颈癌组织放化疗前后长链非编码RNA(lncRNA)的表达谱变化及其临床意义。筛选出与宫颈癌放化疗相关的lncRNA,为宫颈癌的临床放化疗敏感性预测提供依据。方法:取30例宫颈癌患者放化疗前宫颈活检组织和放化疗后手术切除的宫颈组织,应用高通量lncRNA芯片技术分别检测宫颈癌放化疗前后组织中的lncRNA的表达谱变化,并应用RT-PCR技术对结果加以验证。结果:与放化疗前的宫颈癌相比,宫颈癌放化疗组织中共有23 530条lncRNA和14 037个mRNA存在差异性表达。通过GO聚类分析表明:上调mRNA和下调mRNA分别参与多种不同的生物过程。通过进一步分析发现变化差异性最明显的20个lncRNA可能通过影响相应的mRNA来发挥其生物学功能。经RT-PCR验证结果与芯片检测结果相一致。结论:本研究罗列了与宫颈癌放化疗密切相关的lncRNA及相关转录的分子功能、涉及的分子生物学通路等,筛选出了与放化疗密切相关的明显差异表达的lncRNA,为预测宫颈癌放疗敏感性标志物提供分子依据。

Objective:To investigate the different expression profiles of lncRNA in cervical cancer before and after radiotherapy and chemotherapy,so as to select the lncRNAs related with radiotherapy and chemotherapy in cervical cancer and provide the foundation for predicting the sensitivity of radiotherapy and chemotherapy.Methods:In this study,a total of 30 cases of cervical cancer patients were included to assay their biopsy tissues before radiotherapy and chemotherapy and resected tissues by surgery after radiotherapy and chemotherapy.High-throughout lncRNA microarray was used to detect the lncRNA expression profiles of cervical cancer tissues before and after radiotherapy and chemotherapy,then,the results were further verified by real-time quantitative RT-PCR.Results:Compared with cervical cancer tissues before radiotherapy and chemotherapy,a total of23 530 lncRNA and 14 037 mRNA were identified as differentially expressed in cervical cancer tissues after radiotherapy and chemotherapy.GO cluster analysis showed that up-regulated mRNAs and down-regulated mRNAs were associated with various biological processes,respectively.And then,20 lncRNAs with most obvious difference were further analyzed and found to exert their biological functions by influencing relevant mRNA.Finally,results obtained by quantitative PCR were mainly consistent with the microarray.Conclusion:This study listed lncRNAs closely associated with radiotherapy and chemotherapy of cervical cancer,molecular functions of relevant transcripts and involved biological pathways,screened those lncRNAs with significantly different expression related with radiotherapy and chemotherapy,and it might provid molecular basis for predicting cervical cancer markers correlated with the sensitivity to radiotherapy and chemotherapy.