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第42卷第7期                           南京医科大学学报(自然科学版)
                  2022年7月                   Journal of Nanjing Medical University(Natural Sciences)     ·921 ·


               ·基础研究·

                宫内发育迟缓小鼠妊娠期胰岛lncRNA和mRNA的表达谱分析



                王 莉,袁 逸,唐 艺,孙 璐,袁庆新                *

                南京医科大学第一附属医院内分泌科,江苏 南京 210029



               [摘   要] 目的:对正常孕鼠和宫内发育迟缓(intrauterine growth retardation,IUGR)小鼠孕期胰岛RNA进行高通量测序分析,
                筛选出差异表达的长链非编码RNA(long non⁃coding RNA,lncRNA)和信使RNA(messenger RNA,mRNA),为深入探讨IUGR孕
                鼠胰岛功能障碍的发病机制提供理论基础。方法:提取IUGR成年后孕鼠和正常孕鼠胰岛RNA并进行高通量测序,筛选出差
                异表达的lncRNA和mRNA,进行lncRNA和mRNA关联分析,对lncRNA相关的靶mRNA进行GO功能注释分析、KEGG通路富
                集分析,重点关注高差异表达且可能影响孕期胰岛功能的lncRNA。结果:IUGR孕鼠和正常孕鼠差异表达的lncRNA 1 007个,
                其中483个上调,524个下调;差异表达的mRNA 50个,其中22个上调,28个下调。对差异lncRNA的靶mRNA和差异mRNA进
                行功能分析,GO分析示它们参与的生物学途径集中于细胞及组织过程、生物调节、代谢及应激过程;分子功能集中在整合、催
                化活性、转运活性、分子功能调节等方面;KEGG 分析示它们主要集中在代谢、癌症、次生代谢产物的生物合成、PI3K⁃AKT 及
                MAPK 通路。对差异表达的 lncRNA FTX 和 Neat1 进一步分析表明,IUGR 孕鼠和正常孕鼠的 FTX 表达量分别较未孕时下降
               (P < 0.001),而 Neat1上升(P < 0.01);FTX、Neat1表达量在IUGR孕鼠和正常孕鼠间有显著差异(P < 0.05),且表达量受糖浓度
                调节。lncRNA FTX与其靶mRNA均为反式(trans)作用,lncRNA Neat1与Frmd8为顺式(cis)作用,余为trans作用。结论:本研究
                筛选出IUGR孕鼠和正常孕鼠胰岛中差异表达的lncRNA和mRNA,lncRNA通过不同互作关系调控靶mRNA,调节糖代谢过程。
               [关键词] 宫内发育迟缓;lncRNA;mRNA;转录组测序;胰岛功能
               [中图分类号] R714.25                    [文献标志码] A                     [文章编号] 1007⁃4368(2022)07⁃921⁃11
                doi:10.7655/NYDXBNS20220703



                Expression profile of lncRNA and mRNA in islets of pregnant mice born with intrauterine
                growth retardation

                WANG Li,YUAN Yi,TANG Yi,SUN Lu,YUAN Qingxin    *
                Department of Endocrinology,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China


               [Abstract] Objective:High⁃throughput sequencing analysis was performed in adult islets RNAs of normal mice and intrauterine
                growth retardation(IUGR)mice during pregnancy,which screened out differentially expressed long non⁃coding RNA(lncRNA)and
                messenger RNA(mRNA)to provide a theoretical basis for further exploring the pathogenesis of islet dysfunction in pregnant mice born
                with IUGR. Methods:Islet RNAs were extracted from IUGR and normal pregnant mice for high⁃throughput sequencing analysis. The
                differentially expressed lncRNAs and mRNAs were screened and association analysis between them was performed. We conducted
                gene ontology(GO)analyisis,Kyoto encyclopedia of gene and genome(KEGG)enrichment analysis on taget mRNAs of differentially
                expressed lncRNAs. Emphasis was placed on the highly differentially expressed lncRNAs,especially those that may be involved in the
                regulation of islet function during pregnancy. Results:There were 1 007 differentially expressed lncRNAs between IUGR pregnancy
               (IP)and normal pregnancy(NP),among which 483 were up⁃regulated and 524 were down⁃regulated. Fifty mRNAs were differentially
                expressed,of which 22 were up⁃regulated and 28 were down⁃regulated. The GO analysis of differentially expressed lncRNAs’target
                mRNAs and differentially expressed mRNAs showed that biological process(BP)mainly focused on cellular and tissue processes,
                biological regulation,metabolism and stress processes;molecular functions(MF)were concentrated in integration,catalytic activity,
                transport activity,molecular function regulation,etc. KEGG enrichment analysis highlighted the involvement of metabolic pathway,
                cancer pathway,biosynthesis of secondary metabolites,PI3K⁃AKT pathway and MAPK pathway. We furether analysed lncRNA FTX

               [基金项目] 国家自然科学基金(81570697,81170715)
                ∗
                通信作者(Corresponding author),E⁃mail:yqx@njmu.edu.cn
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