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An expanded landscape of human long noncoding RNA.

ABSTRACT: Long noncoding RNAs (lncRNAs) are emerging as key regulators of multiple essential biological processes involved in physiology and pathology. By analyzing the largest compendium of 14,166 samples from normal and tumor tissues, we significantly expand the landscape of human long noncoding RNA with a high-quality atlas: RefLnc (Reference catalog of LncRNA). Powered by comprehensive annotation across multiple sources, RefLnc helps to pinpoint 275 novel intergenic lncRNAs correlated with sex, age or race as well as 369 novel ones associated with patient survival, clinical stage, tumor metastasis or recurrence. Integrated in a user-friendly online portal, the expanded catalog of human lncRNAs provides a valuable resource for investigating lncRNA function in both human biology and cancer development.

SUBMITTER: Jiang S

PROVIDER: S-EPMC6735957 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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An expanded landscape of human long noncoding RNA.

Jiang Shuai S Cheng Si-Jin SJ Ren Li-Chen LC Wang Qian Q Kang Yu-Jian YJ Ding Yang Y Hou Mei M Yang Xiao-Xu XX Lin Yuan Y Liang Nan N Gao Ge G

Nucleic acids research 20190901 15

Long noncoding RNAs (lncRNAs) are emerging as key regulators of multiple essential biological processes involved in physiology and pathology. By analyzing the largest compendium of 14,166 samples from normal and tumor tissues, we significantly expand the landscape of human long noncoding RNA with a high-quality atlas: RefLnc (Reference catalog of LncRNA). Powered by comprehensive annotation across multiple sources, RefLnc helps to pinpoint 275 novel intergenic lncRNAs correlated with sex, age or ...[more]

PMID: 31350901

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Project description:IntroductionThe regenerative capacity of mesenchymal stromal cells or medicinal signaling cells (MSCs) is largely mediated by their secreted small extracellular vesicles (sEVs), and the therapeutic efficacy of sEVs can be enhanced by licensing approaches (e.g., cytokines, hypoxia, chemicals, and genetic modification). Noncoding RNAs within MSC-derived sEVs (MSC-sEVs) have been demonstrated to be responsible for tissue regeneration. However, unlike miRNA fingerprints, which have been explored, the landscape of long noncoding RNAs (lncRNAs) in MSC-sEVs remains to be described.ObjectivesTo characterize lncRNA signatures in sEVs of human adipose-derived MSCs with or without inflammatory cytokine licensing and depict MSC-sEV-specific and MSC-enriched lncRNA repertoires.MethodssEVs were isolated from MSCs with or without TNF-α and IFN-γ (20 ng/mL) stimulation. High-throughput lncRNA sequencing and an in silico approach were employed to analyze the profile of lncRNAs in sEVs and predict lncRNA-protein interactomes.ResultssEVs derived from human MSCs and fibroblasts carried a unique landscape of lncRNAs distinct from the lncRNAs inside these cells. Compared with fibroblast-derived sEVs (F-sEVs), 194 MSC-sEV-specific and 8 upregulated lncRNAs in MSC-sEVs were considered "medicinal signaling lncRNAs"; inflammatory cytokines upregulated 27 lncRNAs in MSC-sEVs, which were considered "licensing-responsive lncRNAs". Based on lncRNA-protein interactome prediction and enrichment analysis, we found that the proteins interacting with medicinal signaling lncRNAs or licensing-responsive lncRNAs have a tight interaction network involved in chromatin remodeling, SWI/SNF superfamily type complexes, and histone binding.ConclusionIn summary, our study depicts the landscape of lncRNAs in MSC-sEVs and predicts their potential functions via the lncRNA-protein interactome. Elucidation of the lncRNA landscape of MSC-sEVs will facilitate defining the therapeutic potency of MSC-sEVs and the development of sEV-based therapeutics.

Dataset Information

An expanded landscape of human long noncoding RNA.

Publications

An expanded landscape of human long noncoding RNA.

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