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Published on: November 2, 2013
Systematic identification of long non-coding RNAs with cancer-testis expression patterns in 14 cancer types
Na Qin1,2,3, Cheng Wang1,2,3,4, Qun Lu2,3
1State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, China.
Abstract:
Cancer-testis (CT) genes are a group of genes that are potential targets of immunotherapy and candidate epi-drivers participating in the development of cancers. Previous studies mainly focused on protein-coding genes, neglecting long non-coding RNAs with the same expression patterns. In this study, we performed a systematic investigation of cancer-testis long non-coding RNAs (CT-lncRNAs) with multiple independent open-access databases.We identified 1,325 extremely highly expressed CT-lncRNAs (EECT-lncRNAs) in 14 cancer types. Functional annotation revealed that CT-lncRNAs reactivated in cancers could promote genome instability and the malignant potential of cancers. We observed a mutually exclusive pattern of EECT-lncRNA activation and mutation in known oncogenes, suggesting their potential role as drivers of cancer that complement known mut-driver genes. Additionally, we provided evidence that testis-specific regulatory elements and promoter hypo-methylation may be EECT-lncRNA activation mechanisms, and EECT-lncRNAs may regulate CT gene reactivation. Taken together, our study puts forth a new hypothesis in the research field of CT genes, whereby CT-lncRNAs/EECT-lncRNAs play important roles in the progression and maintenance of tumorigenesis, expanding candidate CT epi-driver genes from coding genes to non-coding RNAs.
Insights
This study identifies 1,325 cancer-testis long non-coding RNAs (CT-lncRNAs) that promote cancer by increasing genome instability. These CT-lncRNAs may act as novel cancer drivers, complementing known oncogenes.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Cancer-testis (CT) genes are crucial in cancer development and immunotherapy targets.
- Previous research focused on protein-coding CT genes, overlooking non-coding RNAs.
- Long non-coding RNAs (lncRNAs) with CT expression patterns are understudied.
Purpose of the Study:
- To systematically investigate cancer-testis long non-coding RNAs (CT-lncRNAs).
- To identify extremely highly expressed CT-lncRNAs (EECT-lncRNAs) across various cancer types.
- To explore the functional roles and regulatory mechanisms of EECT-lncRNAs in tumorigenesis.
Main Methods:
- Utilized multiple independent open-access databases for comprehensive analysis.
- Performed systematic investigation and functional annotation of identified CT-lncRNAs.
- Analyzed expression patterns, mutations in oncogenes, and regulatory elements.
Main Results:
- Identified 1,325 EECT-lncRNAs across 14 cancer types.
- EECT-lncRNAs promote genome instability and enhance cancer's malignant potential.
- Observed mutual exclusivity between EECT-lncRNA activation and oncogene mutations.
- Identified testis-specific regulatory elements and hypomethylation as potential activation mechanisms.
- Provided evidence for EECT-lncRNA regulation of CT gene reactivation.
Conclusions:
- CT-lncRNAs, particularly EECT-lncRNAs, are significantly involved in cancer progression and maintenance.
- EECT-lncRNAs function as potential cancer drivers, complementing known mutated oncogenes.
- This study expands the scope of CT epi-driver genes to include non-coding RNAs.
- EECT-lncRNAs represent a novel class of biomarkers and therapeutic targets in oncology.
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