College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, Heilongjiang, China.
J Transl Med. 2021 Dec 14;19(1):509. doi: 10.1186/s12967-021-03179-5.
Emerging 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.
In 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.
We 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.
Clarification of the lincRNA genomic clusters specific roles in human cancers could be beneficial for understanding the molecular pathogenesis of different cancer types.
新出现的证据表明，一些长的基因间非编码 RNA（lncRNA）可能在同一染色体上形成簇，lncRNA 基因组簇可能在病理生理机制中发挥关键作用。然而，lncRNA 聚类的全面研究很少，特别是在不同癌症类型中对其功能意义的表征。
在本研究中，我们首先构建了一种基于滑动窗口方法的计算方法，用于系统地识别 lincRNA 基因组簇。然后，我们剖析了这些 lincRNA 基因组簇，以确定在合作表达、不同物种间的保守性、靶向 miRNA 和 CNV 频率方面的共同特征。接下来，我们对来自癌症基因组图谱（TCGA）和基因型组织表达（GTEx）的不同癌症类型的患者的差异表达模式和总生存结果进行了全面分析。最后，我们通过功能富集分析、通路分析和药物-靶标相互作用探索了 lincRNA 基因组簇的潜在机制。
我们根据算法确定了 lincRNA 基因组簇。聚类 lincRNA 倾向于共表达、高度保守、被更多的 miRNA 靶向，并且具有相似的缺失和重复频率，这表明 lincRNA 基因组簇可能通过组合作用发挥作用。我们进一步系统地探索了保守和癌症特异性的 lincRNA 基因组簇，表明它们通过多种途径参与了疾病发生的一些重要机制。此外，lincRNA 基因组簇可以作为具有潜在临床意义的生物标志物，并参与癌症发展中的特定病理过程。此外，在 DLK1-DIO3 印记基因座中发现了一个名为 Cluster127 的 lincRNA 基因组簇，其中包含 MEG3、MEG8、MEG9、MIR381HG、LINC02285、AL132709.5 和 AL132709.1。进一步分析表明，Cluster127 可能具有预测癌症预后的潜力，并通过参与 PI3K-AKT 信号通路的调节发挥作用。
阐明 lincRNA 基因组簇在人类癌症中的特定作用，有助于理解不同癌症类型的分子发病机制。
