Transcriptome profiling of esophageal squamous cell carcinoma reveals a long noncoding RNA acting as a tumor suppressor

// Guifeng Wei 1,2,* , Huaxia Luo 1,2,* , Yu Sun 1,2,* , Jiagen Li 3 , Liqing Tian 1 , Wei Liu 1,2 , Lihui Liu 1,2 , Jianjun Luo 1 , Jie He 3 and Runsheng Chen 1,4 1 Bioinformatics Laboratory and CAS Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China 2 University of Chinese Academy of Sciences, Beijing, China 3 Department of Thoracic Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China 4 Research Network of Computational Biology, RNCB, Beijing, China * These authors have contributed equally to this work Correspondence to: Runsheng Chen, email: // Jie He, email: // Keywords : ESCC, long noncoding RNAs, tumor suppressor, metastasis, Epist Received : March 16, 2015 Accepted : May 02, 2015 Published : May 19, 2015 Abstract Esophageal Squamous Cell Carcinoma (ESCC) is among the most common malignant cancers worldwide. In the past, extensive efforts have been made to characterize the involvement of protein-coding genes in ESCC tumorigenesis but few for long noncoding RNAs (lncRNAs). To investigate the transcriptome profile and functional relevance of lncRNAs, we performed an integrative analysis of a customized combined lncRNA-mRNA microarray and RNA-seq data on ESCCs and matched normal tissues. We identified numerous lncRNAs that were differentially expressed between the normal and tumor tissues, termed “ESCC-associated lncRNAs (ESCALs)”, of which, the majority displayed restricted expression pattern. Also, a subset of ESCALs appeared to be associated with ESCC patient survival. Gene set enrichment analysis (GSEA) further suggested that over half of the ESCALs were positively- or negatively- associated with metastasis. Among these, we identified a novel nuclear-retained lncRNA, named Epist , which is generally highly expressed in esophagus, and which is down-regulated during ESCC progression. Epist over-expression and knockdown studies further suggest that Epist inhibits the metastasis, acting as a tumor suppressor in ESCC. Collectively, our analysis of the ESCC transcriptome identified the potential tumor suppressing lncRNA Epist , and provided a foundation for future efforts to identify functional lncRNAs for cancerous therapeutic targeting.