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
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Creator |
Wu, Peng
Yang, Shuo Singh, Sandeep Qin, Fujun Kumar, Shailesh Wang, Ling Ma, Ding Li, Hui |
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Subject |
Chimeric RNA
Gene fusion Bioinformatics RNA-Seq Cervical cancer |
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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. |
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Date |
2018-11-15T10:43:58Z
2018-11-15T10:43:58Z 2018 |
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Type |
Article
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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 |
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Language |
en_US
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Format |
application/pdf
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Publisher |
Elsevier B.V.
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