Identifying and characterizing lincRNA genomic clusters reveals its cooperative functions in human cancer
Abstract Background 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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-12-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-021-03179-5 |
| _version_ | 1828138800773070848 |
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| author | Hanxiao Zhou Yue Gao Xin Li Shipeng Shang Peng Wang Hui Zhi Shuang Guo Dailin Sun Hongjia Liu Xia Li Yunpeng Zhang Shangwei Ning |
| author_facet | Hanxiao Zhou Yue Gao Xin Li Shipeng Shang Peng Wang Hui Zhi Shuang Guo Dailin Sun Hongjia Liu Xia Li Yunpeng Zhang Shangwei Ning |
| author_sort | Hanxiao Zhou |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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. Results 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. Conclusions Clarification of the lincRNA genomic clusters specific roles in human cancers could be beneficial for understanding the molecular pathogenesis of different cancer types. |
| first_indexed | 2024-04-11T18:42:10Z |
| format | Article |
| id | doaj.art-7b5d1567a120442c8074fb1b563a8838 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-11T18:42:10Z |
| publishDate | 2021-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-7b5d1567a120442c8074fb1b563a88382022-12-22T04:08:57ZengBMCJournal of Translational Medicine1479-58762021-12-0119111510.1186/s12967-021-03179-5Identifying and characterizing lincRNA genomic clusters reveals its cooperative functions in human cancerHanxiao Zhou0Yue Gao1Xin Li2Shipeng Shang3Peng Wang4Hui Zhi5Shuang Guo6Dailin Sun7Hongjia Liu8Xia Li9Yunpeng Zhang10Shangwei Ning11College of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityAbstract Background 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. Methods 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. Results 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. Conclusions Clarification of the lincRNA genomic clusters specific roles in human cancers could be beneficial for understanding the molecular pathogenesis of different cancer types.https://doi.org/10.1186/s12967-021-03179-5LincRNAChromosome physical locationClusteringCoordinated regulationPan cancerClinical prognosis |
| spellingShingle | Hanxiao Zhou Yue Gao Xin Li Shipeng Shang Peng Wang Hui Zhi Shuang Guo Dailin Sun Hongjia Liu Xia Li Yunpeng Zhang Shangwei Ning Identifying and characterizing lincRNA genomic clusters reveals its cooperative functions in human cancer Journal of Translational Medicine LincRNA Chromosome physical location Clustering Coordinated regulation Pan cancer Clinical prognosis |
| title | Identifying and characterizing lincRNA genomic clusters reveals its cooperative functions in human cancer |
| title_full | Identifying and characterizing lincRNA genomic clusters reveals its cooperative functions in human cancer |
| title_fullStr | Identifying and characterizing lincRNA genomic clusters reveals its cooperative functions in human cancer |
| title_full_unstemmed | Identifying and characterizing lincRNA genomic clusters reveals its cooperative functions in human cancer |
| title_short | Identifying and characterizing lincRNA genomic clusters reveals its cooperative functions in human cancer |
| title_sort | identifying and characterizing lincrna genomic clusters reveals its cooperative functions in human cancer |
| topic | LincRNA Chromosome physical location Clustering Coordinated regulation Pan cancer Clinical prognosis |
| url | https://doi.org/10.1186/s12967-021-03179-5 |
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