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长链非编码RNA空间转录组分析揭示组织特异性和癌症中的功能(英文)

Spatial transcriptome analysis of long non-coding RNAs reveals tissue specificity and functional roles in cancer

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【作者】 徐康靳喜云罗芽邹昊哲吕德重王丽萍付丽妹蔡阳阳邵婷婷李永生徐娟

【Author】 Kang XU;Xiyun JIN;Ya LUO;Haozhe ZOU;Dezhong LV;Liping WANG;Limei FU;Yangyang CAI;Tingting SHAO;Yongsheng LI;Juan XU;College of Bioinformatics Science and Technology, Harbin Medical University;Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Biomedical Information and Engineering, Hainan Women and Children’s Medical Center, Hainan Medical University;

【通讯作者】 李永生;徐娟;

【机构】 哈尔滨医科大学生物信息学科学与技术学院海南医学院热带转化医学教育部重点实验室生物医学信息与工程学院海南省妇女儿童医学中心

【摘要】 目的:长链非编码RNA(long non-coding RNAs,lnc RNAs)在维持组织形态和功能方面发挥着重要作用,其精确调控效应与其表达模式密切相关。然而,lnc RNA在人体内的空间表达模式还未得到明确刻画。方法:在本研究中,我们构建了5个完整的人类lnc RNAs转录组图谱,覆盖了数千个正常或疾病状态下的主要组织样本。在不同资源的相同组织中,lnc RNA转录组表现出高度的一致性,在特定组织中则表现出更高的复杂性。在每个资源中都发现了组织升高(tissue-elevated,TE)的lnc RNA,并通过整合分析提炼出了稳定的TE lnc RNA。我们在组织中检测到了1~4684个稳定的TE lnc RNAs,其中TE lnc RNA最多的是睾丸组织,其次是脑组织。TE lnc RNA的功能分析表明,TE lnc RNA在相应的组织相关通路中发挥重要作用。此外,我们发现,稳健的TE lnc RNA的表达特征使其成为区分组织的有效生物标记物;TE lnc RNA也倾向于与癌症相关,表现出差异表达或与患者生存相关。结论:综上所述,lnc RNAs的空间分类是阐明lnc RNAs在维持组织形态和组织限制性疾病进展中功能的重要起点。

【Abstract】 Long non-coding RNAs(lncRNAs) play a significant role in maintaining tissue morphology and functions, and their precise regulatory effectiveness is closely related to expression patterns. However, the spatial expression patterns of lncRNAs in humans are poorly characterized. Here, we constructed five comprehensive transcriptomic atlases of human lncRNAs covering thousands of major tissue samples in normal and disease states. The lncRNA transcriptomes exhibited high consistency within the same tissues across resources, and even higher complexity in specialized tissues. Tissue-elevated(TE) lncRNAs were identified in each resource and robust TE lncRNAs were refined by integrative analysis. We detected 1 to 4684 robust TE lncRNAs across tissues; the highest number was in testis tissue, followed by brain tissue. Functional analyses of TE lncRNAs indicated important roles in corresponding tissue-related pathways. Moreover, we found that the expression features of robust TE lncRNAs made them be effective biomarkers to distinguish tissues; TE lncRNAs also tended to be associated with cancer, and exhibited differential expression or were correlated with patient survival. In summary, spatial classification of lncRNAs is the starting point for elucidating the function of lncRNAs in both maintenance of tissue morphology and progress of tissue-constricted diseases.

【基金】 supported by the National Natural Science Foundation of China (Nos. 31970646, 32060152, 32070673, and 32170676);the Hainan Province Science and Technology Special Fund (No. ZDYF2021SHFZ051);the Harbin Medical University Marshal Initiative Funding (No. HMUMIF-21024);the Marshal Initiative Funding of Hainan Medical University (No. JBGS202103);the Heilongjiang Touyan Innovation Team Program
  • 【文献出处】 Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) ,浙江大学学报B辑(生物医学与生物技术)(英文版) , 编辑部邮箱 ,2023年01期
  • 【分类号】R730
  • 【下载频次】14
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