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Sci Rep. 2016 Nov 28;6:37982. doi: 10.1038/srep37982.

Circular RNAs are down-regulated in KRAS mutant colon cancer cells and can be transferred to exosomes.

Author information

1
Department of Biomedical Informatics, Vanderbilt University, Nashville, Tennessee 37232, USA.
2
Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37232, USA.
3
Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee 37232, USA.
4
Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232, USA.
5
Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
6
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
7
HudsonAlpha Institute for Biotechnology, Huntsville, Alabama 35806, USA.

Abstract

Recent studies have shown that circular RNAs (circRNAs) are abundant, widely expressed in mammals, and can display cell-type specific expression. However, how production of circRNAs is regulated and their precise biological function remains largely unknown. To study how circRNAs might be regulated during colorectal cancer progression, we used three isogenic colon cancer cell lines that differ only in KRAS mutation status. Cellular RNAs from the parental DLD-1 cells that contain both wild-type and G13D mutant KRAS alleles and isogenically-matched derivative cell lines, DKO-1 (mutant KRAS allele only) and DKs-8 (wild-type KRAS allele only) were analyzed using RNA-Seq. We developed a bioinformatics pipeline to identify and evaluate circRNA candidates from RNA-Seq data. Hundreds of high-quality circRNA candidates were identified in each cell line. Remarkably, circRNAs were significantly down-regulated at a global level in DLD-1 and DKO-1 cells compared to DKs-8 cells, indicating a widespread effect of mutant KRAS on circRNA abundance. This finding was confirmed in two independent colon cancer cell lines HCT116 (KRAS mutant) and HKe3 (KRAS WT). In all three cell lines, circRNAs were also found in secreted extracellular-vesicles, and circRNAs were more abundant in exosomes than cells. Our results suggest that circRNAs may serve as promising cancer biomarkers.

PMID:
27892494
PMCID:
PMC5125100
DOI:
10.1038/srep37982
[Indexed for MEDLINE]
Free PMC Article

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