1. Integrative analyses of transcriptome sequencing identify novel functional lncRNAs in esophageal squamous cell carcinoma
- Author
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De-Chen Lin, Xu Ly, H P Koeffler, Liu Yj, Wang Ld, Xu Yj, Lei F, Liao Ld, Li Em, Wang Qy, Feng Cc, Xue Yj, Wang Mr, Zhu Y, Wu Bl, Tang Zd, Li X, Shen Jh, Zhao Jm, Ai B, Li Xc, Zhang J, He Jz, Li M, Wu Zy, Li S, Wang Sh, Cao Hh, Huang Gw, Li Cq, Zheng Cp, Bai Xf, and Wu Jy
- Subjects
0301 basic medicine ,Cancer Research ,Oncology and Carcinogenesis ,Regulator ,Biology ,Bioinformatics ,Malignancy ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,medicine ,2.1 Biological and endogenous factors ,Aetiology ,EP300 ,Molecular Biology ,Gene ,Cancer ,Integrative bioinformatics ,Cell growth ,Human Genome ,RNA ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,Original Article ,Biochemistry and Cell Biology ,Digestive Diseases ,Biotechnology - Abstract
Long non-coding RNAs (lncRNAs) have a critical role in cancer initiation and progression, and thus may mediate oncogenic or tumor suppressing effects, as well as be a new class of cancer therapeutic targets. We performed high-throughput sequencing of RNA (RNA-seq) to investigate the expression level of lncRNAs and protein-coding genes in 30 esophageal samples, comprised of 15 esophageal squamous cell carcinoma (ESCC) samples and their 15 paired non-tumor tissues. We further developed an integrative bioinformatics method, denoted URW-LPE, to identify key functional lncRNAs that regulate expression of downstream protein-coding genes in ESCC. A number of known onco-lncRNA and many putative novel ones were effectively identified by URW-LPE. Importantly, we identified lncRNA625 as a novel regulator of ESCC cell proliferation, invasion and migration. ESCC patients with high lncRNA625 expression had significantly shorter survival time than those with low expression. LncRNA625 also showed specific prognostic value for patients with metastatic ESCC. Finally, we identified E1A-binding protein p300 (EP300) as a downstream executor of lncRNA625-induced transcriptional responses. These findings establish a catalog of novel cancer-associated functional lncRNAs, which will promote our understanding of lncRNA-mediated regulation in this malignancy.
- Published
- 2017