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MIR99AHG:a novel lncRNA host gene with diverse regulatory roles in cancer
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作者 Jiahua Si Xinming Su +6 位作者 Hening Xu Jiayi Gu Yinuo Feng Zehua Wang Yunxuan Xiao Jianqiao Shentu Shiwei Duan 《Clinical Cancer Bulletin》 2024年第1期74-85,共12页
MIR99AHG,a recently discovered long non-coding RNA(lncRNA),serves as the host gene for the miR-99a/let-7c/miR-125b-2 miRNA cluster.The intricate processing of its three introns yields three distinct micro RNAs(miRNAs)... MIR99AHG,a recently discovered long non-coding RNA(lncRNA),serves as the host gene for the miR-99a/let-7c/miR-125b-2 miRNA cluster.The intricate processing of its three introns yields three distinct micro RNAs(miRNAs).Experimental evidence highlights significant variations in MIR99AHG expression across various cancer types,indicating its potential as a diagnostic marker for cancer.Moreover,FOXA1 acts as an upstream regulator,actively promoting MIR99AHG expression.MIR99AHG,in turn,regulates five downstream proteins(ANXA2,PTBP1,MMP9,PBX3,and PHB2),as well as three competing endogenous RNA(ceRNA)axes and three signaling pathways.This broad spectrum of regulatory effects underscores the pivotal role of MIR99AHG in shaping the behavior of cancer cells.In cancer treatment,MIR99AHG’s functions are equally noteworthy.Experimental findings suggest its impact on immune cell activity within the tumor micro-environment and its role in modulating cancer cell resistance to chemotherapeutic drugs.Follow-up studies on patients further confirm the close association between high MIR99AHG expression and poor prognosis across various cancers,exhibiting significant statistical correlations with various pathological behaviors.In summary,MIR99AHG,acting as a multifaceted lncRNA,not only introduces a potential novel marker for cancer diagnosis but also demonstrates significant application value in cancer treatment and prognosis evaluation. 展开更多
关键词 mir99ahg Long non-coding RNA CANCER DIAGNOSIS Treatment
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METTL3介导的LncRNA MIR99AHG通过抑制miR-136-5p表达诱导卵巢颗粒细胞凋亡的机制研究
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作者 常建芳 孙延庆 《中国计划生育和妇产科》 2024年第6期58-64,共7页
目的 研究LncRNA MIR99AHG(MIR99AHG)在化疗药物导致的卵巢颗粒细胞凋亡中的作用及其潜在的调节机制。方法 采集正常女性和卵巢早衰(premature ovarian failure, POF)患者的卵泡液,检测MIR99AHG表达。将卵巢颗粒细胞KGN分为对照组、顺... 目的 研究LncRNA MIR99AHG(MIR99AHG)在化疗药物导致的卵巢颗粒细胞凋亡中的作用及其潜在的调节机制。方法 采集正常女性和卵巢早衰(premature ovarian failure, POF)患者的卵泡液,检测MIR99AHG表达。将卵巢颗粒细胞KGN分为对照组、顺铂组、顺铂+NC shRNA组、顺铂+sh-MIR99AHG组、顺铂+vector组、顺铂+OE-METTL3组、顺铂+OE-METTL3+OE-MIR99AHG组、顺铂+OE-MIR99AHG组、顺铂+NC mimic组、顺铂+miR-136-5p mimic组及顺铂+sh-MIR99AHG+NC inhibitor组和顺铂+sh-MIR99AHG+miR-136-5p inhibitor组。KGN细胞经相应载体或质粒处理后,采用RIP分析MIR99AHG的m6A修饰水平;在线数据库预测MIR99AHG与miR-136-5p的结合位点,并通过荧光素酶报告基因分析进行验证;采用CCK-8和流式细胞术分析KGN细胞的活力和凋亡水平;ELISA检测Caspase-3酶活性;Western blot检测凋亡相关蛋白BCL-2和Bax表达水平。结果 与正常女性相比,POF患者卵泡液中MIR99AHG表达水平显著上调(P<0.001)。与对照组相比,顺铂处理组KGN细胞中MIR99AHG表达显著上调,METTL3表达及蛋白水平显著下调(P<0.05)。与对照组相比,顺铂处理组KGN细胞活力显著降低,细胞凋亡率显著升高(P<0.05);而与NC shRNA组相比,sh-MIR99AHG组KGN细胞活力显著升高,细胞凋亡率显著降低(P<0.05)。RIP分析发现,Anti-m6A抗体下拉复合物中MIR99AHG显著富集。与vector组相比,OE-METTL3组MIR99AHG的m6A水平显著升高,MIR99AHG mRNA表达水平显著降低(P<0.05);OE-METTL3组KGN细胞活力显著升高,细胞凋亡率显著降低(P<0.05);共转染OE-MIR99AHG可逆转OE-METTL3对KGN细胞活力、凋亡及相关蛋白表达的影响。miR-136-5p与MIR99AHGA存在结合位点,MIR99AHGA负调控miR-136-5p表达。与NC-mimic组相比,miR-136-5p mimic组细胞活力及BCL-2蛋白表达明显升高,细胞凋亡率、Caspase-3酶活性及Bax蛋白表达明显降低(P<0.05)。共转染miR-136-5p inhibitor逆转了sh-MIR99AHG对细胞KGN细胞活力、凋亡及相关蛋白表达的影响(P<0.05)。结论 顺铂诱导MIR99AHG在卵巢颗粒细胞中上调,METTL3通过m6A甲基化修饰抑制MIR99AHG表达,促进MIR99AHG靶标miR-136-5p的上调,从而抑制卵巢颗粒细胞凋亡,改善化疗药物顺铂介导的卵巢早衰。 展开更多
关键词 卵巢颗粒细胞 长链非编码mir-99a-let-7c簇宿主基因 N6-甲基腺苷修饰 N6腺苷甲基转移酶样3 微小核糖核酸-136-5p
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口腔鳞状细胞癌预后相关的长链非编码RNA筛选及验证
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作者 刘絮影 李锦存 +3 位作者 翟堃 胡晨 董文 马坚 《口腔医学研究》 北大核心 2025年第2期109-117,共9页
目的:基于口腔癌在线数据库鉴定与口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)预后相关的长链非编码RNA(long non-coding RNA,lncRNA)和mRNA,构建ceRNA网络,分析其在OSCC发生发展中的作用。方法:从癌症基因组图谱(the cancer ge... 目的:基于口腔癌在线数据库鉴定与口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)预后相关的长链非编码RNA(long non-coding RNA,lncRNA)和mRNA,构建ceRNA网络,分析其在OSCC发生发展中的作用。方法:从癌症基因组图谱(the cancer genome atlas program,TCGA)和基因表达综合数据库(gene expression omnibus database,GEO)中筛选出TCGA-OSCC、GSE23558和GSE30784数据集,进行表达谱分析,筛选出差异表达lncRNA和mRNA,并进行生存分析、基因本体论(Gene Ontology,GO)和京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析,确定其与OSCC预后的相关性。利用starBase、miRTarBase数据库预测关键lncRNA及mRNA的共同靶标miRNA,以此构建竞争性内源性RNA(competing endogenous RNA,ceRNA)网络。通过实时荧光定量聚合酶链反应(real-time quantitative PCR,qRT-PCR)检测这些关键lncRNA在OSCC细胞系和肿瘤组织中表达水平。结果:表达谱分析鉴定出23个差异表达lncRNA,其中有6个lncRNA与OSCC患者预后相关;mRNA的表达分析鉴定出282个差异表达mRNA,主要富集在三磷酸鸟苷(guanosine triphosphate,GTP)酶激活剂活性、核苷酸结合寡聚化域(nucletide-binding oligomerization domain,NOD)样受体等信号通路,其中10个差异表达的mRNA与OSCC预后相关。ceRNA网络构建了包括6个lncRNA、10个mRNA和靶向预测的26个miRNA分子网络。qRT-PCR结果显示包含LINC01980在内的5个lncRNA在OSCC细胞中高表达,而MIR99AHG低表达。在OSCC组织中,LINC01980表达水平明显升高,而MIR99AHG表达水平降低。结论:本研究筛选的LINC01980和MIR99AHG与OSCC进展和预后相关,可作为OSCC的生物学标志物进一步探讨。 展开更多
关键词 口腔鳞状细胞癌 长链非编码RNA 预后 LINC01980 mir99ahg
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