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Updated: Dec 18, 2025
Colorectal Cancer Cell Surface Protein Profiling Using an Antibody Microarray and Fluorescence Multiplexing
Published on: September 25, 2011
Landscape characterization of chimeric RNAs in colorectal cancer
Hao Wu1, Sandeep Singh2, Zhongqiu Xie2
1Department of Breast Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, China; Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA; Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, 410013, China.
Abstract:
Gene fusions and their fusion products have been recognized as ideal biomarkers and drug targets for cancer. However, few recurrent gene fusions were found in colorectal cancer (CRC), despite comprehensive studies. We believe that chimeric RNAs, in the absence of chromosomal rearrangement, may represent a new repertoire of biomarkers and/or therapeutic targets in CRC. In this study, we aim to identify such recurrent chimeric RNAs, and investigate their clinical implications. To do so, we performed extensive data mining for chimeric RNAs using The Cancer Genome Atlas CRC RNA-Seq datasets. Multiple filtering criteria were applied, and the landscape of chimeric RNAs at multiple levels, from various angles, was analyzed. Eleven frequent, cancer biased chimeric RNAs were validated. The expression of RRM2-C2orf48 correlates with poor clinical outcomes, while the expression of parental RRM2 and C2orf48 correlates with positive clinical outcomes. Mechanistically, it is a product of cis-splicing between adjacent genes. Silencing of RRM2-C2orf48 resulted in reduced cellular proliferation in colon cancer cells, whereas overexpressed chimera promoted cell proliferation. These findings suggest that frequent chimeric RNAs are present in CRCs, and that chimeric RNAs may have different expression profiles and functions from parental genes, thus representing a new repertoire of biomarkers and therapeutic targets.
Insights
Chimeric RNAs, without chromosomal rearrangement, are identified as potential biomarkers and therapeutic targets in colorectal cancer (CRC). Their expression, like RRM2-C2orf48, impacts patient outcomes and cancer cell proliferation.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Gene fusions are established cancer biomarkers and drug targets.
- Colorectal cancer (CRC) has a limited number of identified recurrent gene fusions.
- Chimeric RNAs, arising without chromosomal rearrangement, present a potential new avenue for CRC research.
Purpose of the Study:
- To identify recurrent chimeric RNAs in colorectal cancer.
- To investigate the clinical implications and functional roles of these chimeric RNAs.
- To explore chimeric RNAs as novel biomarkers and therapeutic targets in CRC.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) CRC RNA-Seq datasets for extensive data mining.
- Applied multiple filtering criteria to identify and analyze chimeric RNAs.
- Validated eleven frequent, cancer-biased chimeric RNAs and investigated their functional impact through gene silencing and overexpression studies.
Main Results:
- Identified and validated eleven frequent, cancer-biased chimeric RNAs in colorectal cancer.
- The chimeric RNA RRM2-C2orf48, a product of cis-splicing, correlates with poor clinical outcomes.
- RRM2-C2orf48 expression promotes colon cancer cell proliferation, while parental gene expression correlates with positive outcomes.
Conclusions:
- Frequent chimeric RNAs exist in colorectal cancer, distinct from traditional gene fusions.
- Chimeric RNAs can exhibit different expression profiles and functions compared to their parental genes.
- These findings highlight chimeric RNAs as a promising new class of biomarkers and therapeutic targets for CRC.
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