首页|宫颈上皮内瘤变3级患者凋亡相关长链非编码RNA表达谱的鉴定

宫颈上皮内瘤变3级患者凋亡相关长链非编码RNA表达谱的鉴定

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目的:长链非编码RNA(long non-coding RNAs,lncRNAs)在肿瘤的发生和发展中发挥重要作用.宫颈上皮内瘤变3级(cervical intraepithelial neoplasia grade 3,CIN3)是宫颈癌中最严重的癌前病变.然而,lncRNAs在CIN3中的作用机制尚未明确.本研究旨在总结CIN3中的lncRNAs表达谱特征,并筛选出凋亡相关lncRNAs.方法:收集CIN3患者的癌组织及癌旁组织标本.通过RNA测序(RNA sequencing,RNA-Seq)鉴定CIN3的lncRNAs差异表达谱,并采用实时反转录聚合酶链反应(real-time reverse transcription PCR,real-time RT-PCR)进行验证.利用基因本体(Gene Ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)对差异表达分子进行功能富集.通过对lncRNAs的顺式和反式调控分析获得潜在的靶基因.此外,本研究通过CuffLinks分析预测了新的转录本和lncRNAs以期发现新的肿瘤调节分子.结果:在CIN3中共发现1 555个差异表达基因、1 562个差异表达mRNAs、241个差异表达ncRNAs和6 616个新预测的差异表达lncRNAs,其中上调和下调最显著的lncRNAs分别是NR_145433.1和ENST00000513672.1.KEGG分析显示lncRNAs潜在靶基因与细胞凋亡通路、代谢通路、p53等肿瘤相关通路密切相关.5个凋亡相关lncRNAs(NR_145433.1、ENST00000510610.2、UC001Kfo.ENST00000602964.1和NR 123733.1)的real-time RT-PCR验证结果与测序结果相符合.结论:提供了全面的CIN3患者lncRNAs表达谱,特别是凋亡相关的lncRNAs表达谱,为宫颈癌的促癌分子机制研究和治疗靶点寻找提供了新的方向和线索.
Identification of apoptosis-related long non-coding RNAs expression profiles in patient with cervical intraepithelial neoplasia 3
Objective:Long non-coding RNAs(lncRNAs)play an essential role in cancer biology.Cervical intraepithelial neoplasia grade 3(CIN3)is the most severe precancerous lesion of cervical cancer.However,the mechanism of multiple lncRNAs in CIN3 has not been studied in-depth and is worth exploring.This study aims to summarize the lncRNA expression profile in CIN 3 and screen for lncRNAs with potential oncogenic effects.Methods:To further clarify the role of lncRNAs in the development of CIN3,this study collected cancer tissue and para-cancer tissue specimens from three CIN3 patients.The RNA sequencing(RNA-Seq)analysis was used to construct expression profiles of lncRNAs and confirmed by real-time reverse transcription PCR(real-time RT-PCR)methods.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were performed with computational methods.We obtained their possible target genes through the cis-and trans-regulatory analysis of the lncRNAs.In addition,this study predicted new transcripts and lncRNAs by Cufflinks analysis and coding potential identification(Coding Potential Calculator)analysis to discover new tumor regulatory molecules.Results:The differential expressions of 1 555 genes,1 562 mRNAs,241 ncRNAs,and 6 616 new predicted-lncRNAs were found.The most prominently up-regulated and down-regulated lncRNAs were NR_145433.1 and ENST00000513672.1,respectively.KEGG analysis revealed that lncRNA-targeted genes were closely related to apoptosis,metabolic,p53 signaling pathway,and other cancer-related pathways.The real-time RT-PCR validation results of 5 apoptosis-related lncRNAs(NR_145433.1,ENST00000510610.2,UC001Kfo,ENST00000602964.1,and NR_123733.1)in cervical cancer were consistent with the sequencing results.Conclusion:This study provides a comprehensive expression profile of lncRNAs in CIN3 patients,particularly the apoptosis-related expression profile of lncRNAs,and provides direction and clues for the study of cervical cancer and the search for potential therapeutic targets.

long non-coding RNAsRNA sequencingcervical intraepithelial neoplasia grade 3cervical cancerapoptosis

刘朝阳、罗伶俐、吴欣仪、王冰琦、王敏、李先平

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中南大学湘雅二医院检验医学科,长沙 410011

中南大学湘雅二医院党委办公室,长沙 410011

湖南省儿童医院检验中心,长沙 410007

长链非编码RNA RNA测序 宫颈上皮内瘤变3级 宫颈癌 细胞凋亡

2024

中南大学学报(医学版)
中南大学

中南大学学报(医学版)

CSTPCD北大核心
影响因子:1.459
ISSN:1672-7347
年,卷(期):2024.49(7)