Background: Gene fusions and fusion products have been proven to be ideal biomarkers and drug targets for cancer. Even though a comprehensive study of cervical cancer has been conducted as part of the Cancer Genome Atlas (TCGA) project, few recurrent gene fusions have been found, and none above 3% of frequency. Methods: We believe that chimeric fusion RNAs generated by intergenic splicing represent a new repertoire of biomarkers and/or therapeutic targets. However, they would be missed when only genome sequences and fusions at DNA level are considered. We performed extensive data mining for chimeric RNAs using both our and TCGA cervical cancer RNA-Seq datasets. Multiple criteria were applied. We analyzed the landscape of chimeric RNAs at various levels, and from different angles. Findings: The chimeric RNA landscape changed as different filters were applied. 15 highly frequent (>10%) chimeric RNAs were identified. LHX6-NDUFA8 was detected exclusively in cervical cancer tissues and Pap smears, but not in normal controls. Mechanistically, it is not due to interstitial deletion, but a product of cis-splicing between adjacent genes. Silencing of another recurrent chimera, SLC2A11-MIF, resulted in cell cycle arrest and reduced cellular proliferation. This effect is unique to the chimera, and not shared by the two parental genes. Interpretation: Highly frequent chimeric RNAs are present in cervical cancers. They can be formed by intergenic splicing. Some have dear implications as potential biomarkers, or for shedding new light on the biology of the disease. (C) 2018 Published by Elsevier B.V.
基金:
Stand Up To Cancer [SU2C-AACR-IRG0409]; National Science Foundation of China [81372806, 81630060]; National Key Research & Development Program of China [2016YFC0902901]
第一作者单位:[1]Huazhong Univ Sci & Technol, Tongji Hosp, Key Lab Canc Invas & Metastasis, Minist Educ China,Tongji Med Coll, Wuhan 430030, Hubei, Peoples R China[2]Univ Virginia, Sch Med, Dept Pathol, Charlottesville, VA 22908 USA
通讯作者:
通讯机构:[2]Univ Virginia, Sch Med, Dept Pathol, Charlottesville, VA 22908 USA[4]Zhengzhou Univ, Sch Basic Med Sci, Zhengzhou 450001, Henan, Peoples R China
推荐引用方式(GB/T 7714):
Wu Peng,Yang Shuo,Singh Sandeep,et al.The Landscape and Implications of Chimeric RNAs in Cervical Cancer[J].EBIOMEDICINE.2018,37:158-167.doi:10.1016/j.ebiom.2018.10.059.
APA:
Wu, Peng,Yang, Shuo,Singh, Sandeep,Qin, Fujun,Kumar, Shailesh...&Li, Hui.(2018).The Landscape and Implications of Chimeric RNAs in Cervical Cancer.EBIOMEDICINE,37,
MLA:
Wu, Peng,et al."The Landscape and Implications of Chimeric RNAs in Cervical Cancer".EBIOMEDICINE 37.(2018):158-167