长链非编码核糖核苷酸HLA-DQA2与不明原因复发性流产的关联  

Association of long-chain non-coding ribonucleotide HLA-DQA2 with unexplained recurrent miscarriage

作　　者：杨丽[1,2,3] 杨静 卜国森[5] 韩锐 腊晓琳[1,2,3,6] YANG Lil;YANG Jing;BU Guosen;HAN Ruil;LA Xiaolinl(Center for Reproductive Medicine,First Affiliated Hospital of Xinjiang Medical University,Urumqi,Xinjiang 830011,China;Research Center for Integrated Prevention and Treatment of Reproductive Diseases and Birth Defects,Urumqi,Xinjiang 83001l,China;Xinjiang Clinical Research Centre for Reproductive Immunology,First Affiliated Hospital of Xinjiang Medical University,Urumqi,Xinjiang 83001l,China;Department of Gynaecology,Fifth Affiliated Hospital of Xinjiang Medical University,Urumqi,Xinjiang 83001l,China;Department of Neurology,First Affiliated Hospital of Xinjiang Medical University,Urumqi,Xinjiang 830011,China;State Key Laboratory of Pathogenesis,Prevention,and Treatment of High Incidence Diseases in Central Asia,Xinjiang Medical University,Urumqi,Xinjiang 83001l,China)

机构地区：[1]新疆医科大学第一附属医院生殖医学中心,新疆乌鲁木齐830011 [2]生殖疾病与出生缺陷综合防治研究中心,新疆乌鲁木齐830011 [3]新疆医科大学第一附属医院新疆生殖免疫临床医学研究中心,新疆乌鲁木齐830011 [4]新疆医科大学第五附属医院妇科,新疆乌鲁木齐830011 [5]新疆医科大学第一附属医院神经内科,新疆乌鲁木齐830011 [6]新疆医科大学省部共建中亚高发病成因与防治国家重点实验室,新疆乌鲁木齐830011

出　　处：《中国优生与遗传杂志》2024年第4期674-680,共7页Chinese Journal of Birth Health & Heredity

基　　金：新疆维吾尔自治区自然科学基金资助项目(2022D01C467);国家自然科学基金地区项目(81960289);新疆医科大学校级重点实验室建设项目“生殖疾病与出生缺陷综合防治研究中心”。

摘　　要：目的通过对不明原因复发性流产(URSA)孕妇绒毛组织的lncRNA比对参考基因组进行注释,探究URSA中潜在的lncRNA生物学靶点。方法收集4例URSA(实验组)和4例选择性终止妊娠(ETP)孕妇(对照组)的绒毛组织样本,使用StringTie处理并预测各转录本,DESeq2获得差异表达lncRNA,Kyoto Encyclopedia of Genes and Genomes(KEGG)富集分析对lncRNA反式调控及lncRNA顺式调控潜在通路进行探索。结果使用4种编码潜能分析方法对候选lncRNA进行进一步的筛选,共有474个共表达转录本,接着DESeq2获得差异表达lncRNA,有705个显著上调lncRNA数目和107个显著下调表达lncRNA数目,对差异表达的lncRNA和所有差异表达的基因进行共表达分析,其中lncRNA反式调控分子功能主要作用在蛋白结合,生物过程发生在细胞外基质组织,存在于细胞表面。KEGG结果显示其主要是作用于lncRNA HLA-DQA2进而富集在金黄色葡萄球菌感染通路。lncRNA顺式调控分子功能主要作用在蛋白结合,生物过程发生在RNA聚合酶对转录的调节,存在于核染色质。KEGG富集结果显示其主要是作用于lncRNA HLA-DQA2以及BIRCT进而富集在弓形体病感染通路。结论lncRNA HLA-DQA2可能通过调控炎症感染信号通路导致不明原因复发性流产,其可能成为潜在的治疗靶点。Objective To explore Potential lncRNA biological targets in unexplained recurrent spontaneous abortions(URSA)by annotating lncRNA from chorionic tissue of Pregnant women with URSA compared to a reference genome.Methods Four URSA(the experimental group)and four pregnant women who had spontaneous abortions(the control group)provided chorionic tissue samples.Each transcript was processed using String Tie,and DESeq2 was used to identify differentially expressed lncRNA.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis was carried out on the lncRNA trans-regulation and lncRNA cis-regulation Potential pathways were investigated.Results Candidate lncRNA were further screened using four coding Potential analysis methods,with a total of 474 co-expressed transcripts,and differentially expressed lncRNA were obtained by DESeq2,with 705 significantly up-regulated lncRNA and 107 down-regulated expressed lncRNA,and co-expression analyses were performed on differentially expressed lncRNA and differentially expressed genes.The molecular function of lncRNA trans-regulation is mainly in protein binding,and the extracellular matrix architecture,which is mostly found on the cell surface,is where the biological process takes place.KEGG results showed that it mainly acts on the lncRNA HLA-DQA2 which in turn is enriched in the Staphylococcus aureus infectious pathway.The primary molecular function of lncRNA cis-regulation is protein binding,and the biological process takes place in the RNA It primarily affects the lncRNA HLA-DQA2 and BIRCT,according to the KEGG enrichment data,and it is enriched in the Toxoplasma gondii infection pathway.Conclusion lncRNA HLA-DQA2 may cause unexplained recurrent miscarriages by regulating the inflammatory infection signaling pathway,and it may be a Potential therapeutic target.

关 键 词：不明原因复发性流产 绒毛组织 长链非编码RNA 转录组测序 

分 类 号：R714.21[医药卫生—妇产科学]