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The landscape and implications of chimeric RNAs in cervical cancer

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Title The landscape and implications of chimeric RNAs in cervical cancer
 
Creator Wu, Peng
Yang, Shuo
Singh, Sandeep
Qin, Fujun
Kumar, Shailesh
Wang, Ling
Ma, Ding
Li, Hui
 
Subject Chimeric RNA
Gene fusion
Bioinformatics
RNA-Seq
Cervical cancer
 
Description Accepted date: 24 October 2018
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 (N10%) 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 clear implications as potential biomarkers, or for shedding new light on the biology of the
disease.
Fund: Stand Up To Cancer and the National Science Foundation of China
This work was supported by Stand Up To Cancer SU2C-AACRIRG0409
(HL), the National Science Foundation of China (Grants
81372806, 81630060)(PW and DM), and the National Key Research &
Development Program of China (2016YFC0902901) (DM). The funding
agencies had no roles in the experimental design, writing of the manuscript
or the decision to submit. None of the authors were paid by any
pharmaceutical company or other agency for the writing of the article.
HL and DM had full access to all the data in the study and had final responsibility
for the decision to submit for publication.
 
Date 2018-11-15T10:43:58Z
2018-11-15T10:43:58Z
2018
 
Type Article
 
Identifier EBioMedicine, 37: 158-167
2352-3964
http://223.31.159.10:8080/jspui/handle/123456789/898
https://www.sciencedirect.com/science/article/pii/S2352396418304778?via%3Dihub
https://doi.org/ 10.1016/j.ebiom.2018.10.059
 
Language en_US
 
Format application/pdf
 
Publisher Elsevier B.V.