Identifying and characterizing lincRNA genomic clusters reveals its cooperative functions in human cancer

Journal of Translational Medicine

Yue Gao¹  Yunpeng Zhang¹  Hui Zhi¹  Xin Li¹  Hanxiao Zhou¹  Xia Li¹  Shuang Guo¹  Dailin Sun¹  Shipeng Shang¹  Shangwei Ning¹  Hongjia Liu¹  Peng Wang¹ 

[1] College of Bioinformatics Science and Technology, Harbin Medical University, 150081, Harbin, Heilongjiang, China;

关键词: LincRNA;    Chromosome physical location;    Clustering;    Coordinated regulation;    Pan cancer;    Clinical prognosis;   

DOI  :  10.1186/s12967-021-03179-5

来源: Springer

【 摘 要 】

BackgroundEmerging evidence has revealed that some long intergenic non-coding RNAs (lincRNAs) are likely to form clusters on the same chromosome, and lincRNA genomic clusters might play critical roles in the pathophysiological mechanism. However, the comprehensive investigation of lincRNA clustering is rarely studied, particularly the characterization of their functional significance across different cancer types.MethodsIn this study, we firstly constructed a computational method basing a sliding window approach for systematically identifying lincRNA genomic clusters. We then dissected these lincRNA genomic clusters to identify common characteristics in cooperative expression, conservation among divergent species, targeted miRNAs, and CNV frequency. Next, we performed comprehensive analyses in differentially-expressed patterns and overall survival outcomes for patients from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) across multiple cancer types. Finally, we explored the underlying mechanisms of lincRNA genomic clusters by functional enrichment analysis, pathway analysis, and drug-target interaction.ResultsWe identified lincRNA genomic clusters according to the algorithm. Clustering lincRNAs tended to be co-expressed, highly conserved, targeted by more miRNAs, and with similar deletion and duplication frequency, suggesting that lincRNA genomic clusters may exert their effects by acting in combination. We further systematically explored conserved and cancer-specific lincRNA genomic clusters, indicating they were involved in some important mechanisms of disease occurrence through diverse approaches. Furthermore, lincRNA genomic clusters can serve as biomarkers with potential clinical significance and involve in specific pathological processes in the development of cancer. Moreover, a lincRNA genomic cluster named Cluster127 in DLK1-DIO3 imprinted locus was discovered, which contained MEG3, MEG8, MEG9, MIR381HG, LINC02285, AL132709.5, and AL132709.1. Further analysis indicated that Cluster127 may have the potential for predicting prognosis in cancer and could play their roles by participating in the regulation of PI3K-AKT signaling pathway.ConclusionsClarification of the lincRNA genomic clusters specific roles in human cancers could be beneficial for understanding the molecular pathogenesis of different cancer types.

【 授权许可】

CC BY