期刊
ONCOTARGET
卷 4, 期 11, 页码 2135-2143出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.1465
关键词
Transcriptome; transcription-induced chimeric RNAs; GOLM1-MAK10; secreted fusion protein; cancer biomarker; esophageal cancer
资金
- National Natural Science Foundation of China [81071736, 30973508]
- Research Fund for the Doctoral Program of Higher Education of China (RFDP) [20104402110005]
- DOD [W81XWH-10-10327]
- OCRF [PPD/BCM/01.12]
- NIH [R01EB013584]
- PCF Young Investigator award
It is increasingly recognized that chimeric RNAs may exert a novel layer of cellular complexity that contributes to oncogenesis and cancer progression, and could be utilized as molecular biomarkers and therapeutic targets. To date yet no fusion chimeric RNAs have been identified in esophageal cancer, the 6th most frequent cause of cancer death in the world. While analyzing the expression of 32 recurrent cancer chimeric RNAs in esophageal squamous cell carcinoma (ESCC) from patients and cancer cell lines, we identified GOLM1-MAK10, as a highly cancer-enriched chimeric RNA in ESCC. In situ hybridization revealed that the expression of the chimera is largely restricted to cancer cells in patient tumors, and nearly undetectable in non-neoplastic esophageal tissue from normal subjects. The aberrant chimera closely correlated with histologic differentiation and lymph node metastasis. Furthermore, we demonstrate that chimera GOLM1-MAK10 encodes a secreted fusion protein. Mechanistic studies reveal that GOLM1-MAK10 is likely derived from transcription read-through/splicing rather than being generated from a fusion gene. Collectively, these findings provide novel insights into the molecular mechanism involved in ESCC and provide a novel potential target for future therapies. The secreted fusion protein translated from GOLM1-MAK10 could also serve as a unique protein signature detectable by standard non-invasive assays. These observations are critical as there is no clinically useful molecular signature available for detecting this deadly disease or monitoring the treatment response.
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