Transcriptome profiling of esophageal squamous cell carcinoma reveals a long noncoding RNA acting as a tumor suppressor
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Guifeng Wei1,2,*, Huaxia Luo1,2,*, Yu Sun1,2,*, Jiagen Li3, Liqing Tian1, Wei Liu1,2, Lihui Liu1,2, Jianjun Luo1, Jie He3 and Runsheng Chen1,4
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
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
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.
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