Falzone Luca, Scola Letizia, Zanghì Antonino, Biondi Antonio, Di Cataldo Antonio, Libra Massimo, Candido Saverio
Department of Biomedical and Biotechnological Sciences, University of Catania, Catania 95123, Italy.
Department of Pathobiology and Medical Biotechnologies, University of Palermo, Palermo 90127, Italy.
Aging (Albany NY). 2018 May 18;10(5):1000-1014. doi: 10.18632/aging.101444.
Colorectal cancer (CRC) is one of the leading cause of cancer death worldwide. Currently, no effective early diagnostic biomarkers are available for colorectal carcinoma. Therefore, there is a need to discover new molecules able to identify pre-cancerous lesions. Recently, microRNAs (miRNAs) have been associated with the onset of specific pathologies, thus the identification of miRNAs associated to colorectal cancer may be used to detect this pathology at early stages. On these bases, the expression levels of miRNAs were analyzed to compare the miRNAs expression levels of colorectal cancer samples and normal tissues in several miRNA datasets. This analysis revealed a group of 19 differentially expressed miRNAs. To establish the interaction between miRNAs and the most altered genes in CRC, the mirDIP gene target analysis was performed in such group of 19 differentially expressed miRNAs. To recognize miRNAs able to activate or inhibit genes and pathways involved in colorectal cancer development DIANA-mirPath prediction analysis was applied. Overall, these analyses showed that the up-regulated hsa-miR-183-5p and hsa-miR-21-5p, and the down-regulated hsa-miR-195-5p and hsa-miR-497-5p were directly related to colorectal cancer through the interaction with the Mismatch Repair pathway and Wnt, RAS, MAPK, PI3K, TGF-β and p53 signaling pathways involved in cancer development.
结直肠癌(CRC)是全球癌症死亡的主要原因之一。目前,尚无有效的早期诊断生物标志物可用于结直肠癌。因此,需要发现能够识别癌前病变的新分子。最近,微小RNA(miRNA)已与特定病理的发生相关联,因此鉴定与结直肠癌相关的miRNA可用于在早期阶段检测这种病理。基于这些,在几个miRNA数据集中分析了miRNA的表达水平,以比较结直肠癌样本和正常组织的miRNA表达水平。该分析揭示了一组19个差异表达的miRNA。为了建立miRNA与CRC中变化最大的基因之间的相互作用,对这组19个差异表达的miRNA进行了mirDIP基因靶标分析。为了识别能够激活或抑制参与结直肠癌发展的基因和途径的miRNA,应用了DIANA-mirPath预测分析。总体而言,这些分析表明,上调的hsa-miR-183-5p和hsa-miR-21-5p,以及下调的hsa-miR-195-5p和hsa-miR-497-5p通过与错配修复途径以及参与癌症发展的Wnt、RAS、MAPK、PI3K、TGF-β和p53信号通路相互作用,与结直肠癌直接相关。