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Updated: Feb 3, 2026
Author Spotlight: Exploring the Role of FAM83A in Cervical Cancer
Published on: February 9, 2024
The Landscape and Implications of Chimeric RNAs in Cervical Cancer
Peng Wu1, Shuo Yang2, Sandeep Singh3
1The Key Laboratory of Cancer Invasion and Metastasis of the Ministry of Education of China, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
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 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.
Insights
Highly frequent chimeric RNAs, formed by intergenic splicing, were identified in cervical cancer. These novel biomarkers, like LHX6-NDUFA8, show potential for diagnosis and therapeutic targeting in cancer research.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Gene fusions are established cancer biomarkers and drug targets.
- Previous studies of cervical cancer, including TCGA, found limited recurrent gene fusions.
Purpose of the Study:
- To identify novel chimeric RNAs resulting from intergenic splicing as potential biomarkers and therapeutic targets in cervical cancer.
- To explore the landscape of chimeric RNAs missed by DNA-level analyses.
Main Methods:
- Extensive data mining of chimeric RNAs from cervical cancer RNA-Seq datasets (own and TCGA).
- Application of multiple filtering criteria to analyze chimeric RNA landscape.
- Investigation of specific chimeric RNAs' formation and functional impact.
Main Results:
- Identified 15 highly frequent chimeric RNAs (>10%) in cervical cancer.
- LHX6-NDUFA8 was found exclusively in cervical cancer tissues and Pap smears.
- Silencing of SLC2A11-MIF chimera caused cell cycle arrest and reduced proliferation, distinct from parental genes.
Conclusions:
- Cervical cancers harbor frequent chimeric RNAs formed by intergenic splicing.
- These chimeric RNAs have potential as biomarkers and offer new insights into cervical cancer biology.
- The findings highlight the importance of considering RNA-level events for cancer research.
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