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.
概要
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。
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Acknowledgments
This work was 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), and the Heilongjiang Touyan Innovation Team Program.
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Juan XU and Yongsheng LI designed the study. Kang XU, Xiyun JIN, and Ya LUO analyzed and interpreted the data. Kang XU, Haozhe ZOU, Dezhong LV, Liping WANG, and Yangyang CAI performed the cancer analysis. Kang XU, Limei FU, Tingting SHAO, and Yangyang CAI designed the figures. Kang XU, Juan XU, Yongsheng LI, and Tingting SHAO wrote and edited manuscript. All authors have read and approved the final manuscript, and therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.
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Kang XU, Xiyun JIN, Ya LUO, Haozhe ZOU, Dezhong LV, Liping WANG, Limei FU, Yangyang CAI, Tingting SHAO, Yongsheng LI, and Juan XU declare that they have no conflict of interest.
This article does not contain any studies with human or animal subjects performed by any of the authors.
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Xu, K., Jin, X., Luo, Y. et al. Spatial transcriptome analysis of long non-coding RNAs reveals tissue specificity and functional roles in cancer. J. Zhejiang Univ. Sci. B 24, 15–31 (2023). https://doi.org/10.1631/jzus.B2200206
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DOI: https://doi.org/10.1631/jzus.B2200206