Circular RNAs are down-regulated in KRAS mutant colon cancer cells and can be transferred to exosomes.
Circular RNAs are down-regulated in KRAS mutant colon cancer cells and can be transferred to exosomes.
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DOI：
10.1038/srep37982
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发表时间：
2016-11-28
影响因子：
4.6
通讯作者：
Zhang B
中科院分区：
文献类型：
--
作者：
Dou Y;Cha DJ;Franklin JL;Higginbotham JN;Jeppesen DK;Weaver AM;Prasad N;Levy S;Coffey RJ;Patton JG;Zhang B
近年来的研究表明，环状RNA（circular RNA，circRNA）在哺乳动物中含量丰富、广泛表达，并具有细胞类型特异性表达。然而，circRNA的产生是如何被调节的以及它们的精确生物学功能在很大程度上仍然未知。为了研究circRNA在结直肠癌进展过程中如何调节，我们使用了三种仅在KRAS突变状态上不同的同基因结肠癌细胞系。使用RNA-Seq分析来自含有野生型和G13D突变KRAS等位基因两者的亲本DLD-1细胞和同基因匹配的衍生细胞系DKO-1（仅突变KRAS等位基因）和DK-8（仅野生型KRAS等位基因）的细胞RNA。我们开发了一个生物信息学管道来从RNA-Seq数据中识别和评估circRNA候选物。在每个细胞系中鉴定出数百种高质量的circRNA候选物。值得注意的是，与DK-8细胞相比，在DLD-1和DKO-1细胞中，circRNA在整体水平上显著下调，表明突变KRAS对circRNA丰度的广泛影响。这一发现在两个独立的结肠癌细胞系HCT 116（KRAS突变体）和HKe3（KRAS WT）中得到证实。在所有三种细胞系中，在分泌的细胞外囊泡中也发现了circRNA，并且circRNA在外泌体中比细胞中更丰富。我们的研究结果表明，circRNA可能作为有前途的癌症生物标志物。
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.
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影响因子：
7.7
作者：
Katz Y;Li F;Lambert NJ;Sokol ES;Tam WL;Cheng AW;Airoldi EM;Lengner CJ;Gupta PB;Yu Z;Jaenisch R;Burge CB
通讯作者：
Burge CB
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
14.9
作者：
Cook KB;Kazan H;Zuberi K;Morris Q;Hughes TR
通讯作者：
Hughes TR
影响因子：
4.6
作者：
Bachmayr-Heyda A;Reiner AT;Auer K;Sukhbaatar N;Aust S;Bachleitner-Hofmann T;Mesteri I;Grunt TW;Zeillinger R;Pils D
通讯作者：
Pils D