Systematic identification of long non-coding RNAs with cancer-testis expression patterns in 14 cancer types

Na Qin; Cheng Wang; Qun Lu; Zijian Ma; Juncheng Dai; Hongxia Ma; Guangfu Jin; Hongbing Shen; Zhibin Hu

doi:10.18632/oncotarget.21930

Systematic identification of long non-coding RNAs with cancer-testis expression patterns in 14 cancer types

Oncotarget. 2017 Oct 19;8(55):94769-94779. doi: 10.18632/oncotarget.21930. eCollection 2017 Nov 7.

Authors

Na Qin^{1

2

3}, Cheng Wang^{1

2

3

4}, Qun Lu^{2

3}, Zijian Ma^{2

3}, Juncheng Dai^{1

2

3}, Hongxia Ma^{1

2

3}, Guangfu Jin^{1

2

3}, Hongbing Shen^{1

2

3}, Zhibin Hu^{1

2

3}

Affiliations

¹ State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, China.
² Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
³ Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing 211166, China.
⁴ Department of Bioinformatics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211116, 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.

Keywords: cancer-testis gene; genomic instability; long non-coding RNA; lung adenocarcinoma.