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Identifying Cancer Driver lncRNAs Bridged by Functional Effectors through Integrating Multi-omics Data in Human Cancers
- Source :
- Molecular Therapy: Nucleic Acids, Vol 17, Iss , Pp 362-373 (2019)
- Publication Year :
- 2019
- Publisher :
- Elsevier, 2019.
-
Abstract
- The accumulation of somatic driver mutations in the human genome enables cells to gradually acquire a growth advantage and contributes to tumor development. Great efforts on protein-coding cancer drivers have yielded fruitful discoveries and clinical applications. However, investigations on cancer drivers in non-coding regions, especially long non-coding RNAs (lncRNAs), are extremely scarce due to the limitation of functional understanding. Thus, to identify driver lncRNAs integrating multi-omics data in human cancers, we proposed a computational framework, DriverLncNet, which dissected the functional impact of somatic copy number alteration (CNA) of lncRNAs on regulatory networks and captured key functional effectors in dys-regulatory networks. Applying it to 5 cancer types from The Cancer Genome Atlas (TCGA), we portrayed the landscape of 117 driver lncRNAs and revealed their associated cancer hallmarks through their functional effectors. Moreover, lncRNA RP11-571M6.8 was detected to be highly associated with immunotherapeutic targets (PD-1, PD-L1, and CTLA-4) and regulatory T cell infiltration level and their markers (IL2RA and FCGR2B) in glioblastoma multiforme, highlighting its immunosuppressive function. Meanwhile, a high expression of RP11-1020A11.1 in bladder carcinoma was predictive of poor survival independent of clinical characteristics, and CTD-2256P15.2 in lung adenocarcinoma responded to the sensitivity of methyl ethyl ketone (MEK) inhibitors. In summary, this study provided a framework to decipher the mechanisms of tumorigenesis from driver lncRNA level, established a new landscape of driver lncRNAs in human cancers, and offered potential clinical implications for precision oncology. Keywords: cancer drivers, long non-coding RNAs, copy number alterations, cancer hallmarks, immunosuppression
- Subjects :
- Therapeutics. Pharmacology
RM1-950
Subjects
Details
- Language :
- English
- ISSN :
- 21622531
- Volume :
- 17
- Issue :
- 362-373
- Database :
- Directory of Open Access Journals
- Journal :
- Molecular Therapy: Nucleic Acids
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.732bb709ae1c49f4a0041720744e2819
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.omtn.2019.05.030