Dataset Information

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

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.

SUBMITTER: Dou Y

PROVIDER: S-EPMC5125100 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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

Dou Yongchao Y Cha Diana J DJ Franklin Jeffrey L JL Higginbotham James N JN Jeppesen Dennis K DK Weaver Alissa M AM Prasad Nripesh N Levy Shawn S Coffey Robert J RJ Patton James G JG Zhang Bing B

Scientific reports 20161128

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 an ...[more]

PMID: 27892494

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Project description:RNA in milk exosomes can be absorbed in the mammalian intestinal tract and function in gene expression regulations. Our previous work demonstrated that porcine milk exosomes (PME) contain large amounts of miRNAs and mRNAs. Increasing evidence suggests that long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are of particular interest, given their key role in diverse biological processes of animals. However, the expression profiles and the potential functions of lncRNAs and circRNAs in PME are still unknown. In the present study, we isolated PME by ultracentrifugation and performed a comprehensive analysis of lncRNA and circRNA in PME by using RNA sequencing. As a result, 2,466 novel lncRNAs, 809 annotated lncRNAs, and 61 circRNAs were identified in PME. The lncRNAs shared similar characteristics with other mammals in terms of length, exon number, and open reading frames. However, lncRNAs showed a higher level compared with mRNAs. Eight lncRNAs and five circRNAs in PME were selected for PCR identification. A functional enrichment analysis on the target genes of lncRNAs indicated that these genes were involved in cellular macromolecule metabolic, RNA metabolic, and immune processes. The circRNAs host genes were enriched in nucleic acid binding and adherence junction. We also evaluated the potential interaction targets between miRNAs and PME lncRNAs or circRNAs, and the results showed that the PME lncRNAs and the circRNAs have a high density of miRNA target sites. The top 20 highly expressed lncRNAs were found to interact with the proliferation-related miRNAs, and the circRNAs potentially targeted many miRNAs that are associated with the intestinal barrier. This study is the first to provide a resource for lncRNA and circRNA research of porcine milk. Moreover, the potential interaction between lncRNA/circRNA and miRNA is revealed. The present study expands our knowledge of non-coding RNAs in milk, and additional research is necessary to confirm their exactly physiological functions.

Dataset Information

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

Publications

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

Similar Datasets

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