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Journal of Zhejiang University SCIENCE B

ISSN 1673-1581(Print), 1862-1783(Online), Monthly

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

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.

Key words: Spatial expression; Transcriptome; Long non-coding RNA; Cancer; Biomarker

Chinese Summary  <90> 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

徐康1,靳喜云1,罗芽1,邹昊哲1,吕德重1,王丽萍1,付丽妹1,蔡阳阳1,邵婷婷1,李永生2,徐娟1
1哈尔滨医科大学生物信息学科学与技术学院,中国哈尔滨市,150081
2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,中国海口市,571199
目的:长链非编码RNA(long non-coding RNAs,lncRNAs)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,lncRNA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lncRNAs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,lncRNA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lncRNA,并通过整合分析提炼出了稳定的TE lncRNA。我们在组织中检测到了1~4684个稳定的TE lncRNAs,其中TE lncRNA最多的是睾丸组织,其次是脑组织。TE lncRNA的功能分析表明,TE lncRNA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 lncRNA的表达特征使其成为区分组织的有效生物标记物;TE lncRNA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,lncRNAs的空间分类是阐明lncRNAs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。

关键词组:空间表达;转录组;长链非编码RNA(lncRNA);癌症;生物标志物


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DOI:

10.1631/jzus.B2200206

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On-line Access:

2023-01-10

Received:

2022-04-08

Revision Accepted:

2022-07-13

Crosschecked:

2023-01-16

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