INSERM U1078-ECLA, Université de Bretagne Occidentale, SFR ScInBioS, Faculté de Médecine, 22, Avenue Camille Desmoulins, 29200 Brest, France.
INSERM U1078-ECLA, Université de Bretagne Occidentale, SFR ScInBioS, Faculté de Médecine, 22, Avenue Camille Desmoulins, 29200 Brest, France; CHRU de Brest, 5, Avenue Foch, 29200 Brest, France.
Eur J Cancer. 2015 Feb;51(3):409-20. doi: 10.1016/j.ejca.2014.12.007. Epub 2015 Jan 10.
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.
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.
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.
结直肠癌（CRC）主要由结直肠腺瘤（CRAs）发展而来。microRNAs（miRs）是短的非编码转录物，通过与靶 mRNAs 结合来调节基因表达，从而阻止其表达。有人认为，miRs 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。我们通过微阵列和定量逆转录-聚合酶链反应（RT-PCR）（RT-qPCR）对 CRA 和 CRC 中的 miRNA 及其一些靶 mRNAs 的表达进行了分析，与正常粘膜（NOR）进行比较，以鉴定参与 CRC 进展的候选 miRNA。
微阵列分析，以及通过 RT-qPCR 进行的验证分析，显示在结直肠病变中，有 17 个 miRNA 显著下调。虽然，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，但其他 miRNA 是新的（miR-125a-5p 和 miR-320 家族）。一些 miRNA 是 CRC 与 NOR 比较特异性的（miR-320b），或 CRA 与 NOR 比较特异性的（miR-15b 或 miR-16），但其中一些 miRNA（miR-21、miR-24、miR-145、mir-150、miR-378）在 CRA 和 CRC 中与 NOR 相比均下调。这些 miRNA 表达变化对靶基因的影响，提示这些基因在 CRA 和 CRC 中的失调。
我们证实了几种 miRNA 在结直肠病变中异常表达，鉴定了新的失调的 miRNA，并表明几种 miRNA 可以标记从 NOR 到 CRA 的转变，从而标志着癌症早期阶段的进展。
