期刊
CANCER LETTERS
卷 501, 期 -, 页码 1-11出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2020.10.052
关键词
Chimeric RNA; Esophageal squamous cell carcinoma; Sternness; Metastasis
类别
资金
- National Natural Science Foundation of China [82072683, 81773087, 81071736, 81572876, 30973508, 82002491]
- Natural Science Foundation of Guangdong Province of China [9151018004000000]
- Science and Technology Planning Project of Guangdong Province of China [2019A030317024]
- Special Project on the Integration of Industry, Education and Research of Guangdong Province [2011A090100024]
- China Postdoctoral Science Foundation [2020M673078]
- Flagship specialty construction project-General surgery [711003]
This study revealed an undocumented function of chimeric RNAs in aggravating cancer stemness and metastasis.
Transcription-induced chimeric RNAs are an emerging area of research into molecular signatures for disease biomarker and therapeutic target development. Despite their importance, little is known for chimeric RNAs-relevant roles and the underlying mechanisms for cancer pathogenesis and progression. Here we describe a unique ASTN2-PAPPA(antisense) chimeric RNA (A-P-as chiRNA) that could be the first reported chimeric RNA derived from the splicing of exons and intron antisense of two neighboring genes, respectively. Aberrant A-P-as chiRNA level in ESCC tissues was associated with tumor progression and patients' outcome. In vitro and in vivo studies demonstrated that A-P-as chiRNA aggravated ESCC metastasis and enhanced stemness through modulating OCT4. Mechanistic studies demonstrated that ERK5-mediated non-canonical PAF1 activity was required for A-P-as chiRNA-induced cancer malignancy. The study defined an undocumented function of chimeric RNAs in aggravating cancer stemness and metastasis.
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