MicroRNA and targeted mRNA expression profiling analysis in human colorectal adenomas and adenocarcinomas

MicroRNA and targeted mRNA expression profiling analysis in human colorectal adenomas and adenocarcinomas
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DOI:
10.1016/j.ejca.2014.12.007
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发表时间:
2015-02-01
影响因子:
8.4
通讯作者:
Corcos, Laurent
Corcos, Laurent
中科院分区:
医学1区
文献类型:
--
作者:
Gattolliat, Charles-Henry;Uguen, Arnaud;Corcos, Laurent

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背景:结直肠癌(Colorectal cancer,CRC)主要由结直肠腺瘤(colorectal adenomas,CRA)发展而来.微小RNA(miRs)是短的非编码转录物,其通过与靶mRNA结合来调节基因表达,从而阻止其表达。提示miR作为肿瘤抑制因子或癌基因参与癌症,因此也是潜在的癌症生物标志物。我们进行了一个表达分析的miRNA和他们的几个目标mRNA,通过使用微阵列和定量逆转录-聚合酶链反应(RT-PCR)(RT-qPCR),在CRA和CRC,相比,正常粘膜(NOR),以确定候选的miRNA参与CRC progress.Results:微阵列,连同验证性RT-qPCR分析,显示17个显着失调的miRNA在结直肠病变。正如预期的那样,一些miRNA先前已被报道与CRC相关,包括miR-21和miR-145,其他的是新的(miR-125 a-5 p和miR-320家族)。一些miRNA对CRC与NOR的比较(miR-320 b)或CRA与NOR的比较(miR-15 b或miR-16)是特异性的,但与NOR相比,其中几种(miR-21、miR-24、miR-145、miR-150、miR-378)在CRA和CRC中都是去调控的。这些变化的影响,在靶基因的miR表达的建议,这些基因在CRA和CRC.Conclusions的相关失调:我们证实,几个miRNA异常表达在结直肠病变,确定了新的失调的miR,并表明,几个miRNA可以标记从NOR到CRA的过渡,从而标志着从癌症的早期步骤的进展。(C)2014爱思唯尔有限公司版权所有。
Background: Colorectal cancer (CRC) mainly develops from colorectal adenomas (CRAs). MicroRNAs (miRs) are short non-coding transcripts that regulate gene expression by binding to target mRNAs, preventing their expression. It was suggested that miRs were involved in cancer as tumour suppressors or oncogenes, thereby being also potential cancer biomarkers. We conducted an expression analysis of miRNAs and several of their target mRNAs, by using microarrays and quantitative Reverse Transcription-Polymerase Chain Reaction (RT-PCR) (RT-qPCR), in CRA and CRC, as compared to normal mucosa (NOR), in order to identify candidate miRNAs involved in CRC progression.Results: Microarray, together with confirmatory RT-qPCR analyses, showed 17 significantly deregulated miRNAs in colorectal lesions. While, as expected, some miRNAs have been previously reported to be associated with CRC, including miR-21 and miR-145, others were new (miR-125a-5p and miR-320 family). Some miRNAs were specific for the CRC versus NOR comparison (miR-320b), or for the CRA versus NOR comparison (miR-15b or miR-16), but several of them (miR-21, miR-24, miR-145, mir-150, miR-378) were deregulated in both CRAs and CRCs, as compared to NOR. The impact of these changes in miR expression on target genes is suggested by the associated deregulation of these genes in CRA and CRC.Conclusions: We confirmed that several miRNAs were abnormally expressed in colorectal lesions, identified new deregulated miRs, and showed that several miRNAs could mark the transition from NOR to CRA, thereby marking progression from the early steps of cancer. (C) 2014 Elsevier Ltd. All rights reserved.