BACKGROUND Colorectal cancer (CRC) ranks the third among the most common malignancies globally. It is well known that microRNAs (miRNAs) play vital roles in destabilizing mRNAs and repressing their translations in this disease. However, the mechanism of miRNA-induced mRNA cleavage remains to be investigated. METHOD In this study, high-throughput small RNA (sRNA) sequencing was utilized to identify and profile miRNAs from six pairs of colorectal cancer tissues (CTs) and adjacent tissues (CNs). Degradome sequencing (DS) was employed to detect the cleaved target genes. The Database for Annotation, Visualization and Integrated Discovery (DAVID) software was used for GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis. RESULTS In total, 1278 known miRNAs (clustered into 337 families) and 131 novel miRNAs were characterized in the CT and CN libraries, respectively. Of those, 420 known and eight novel miRNAs were defined as differentially expressed miRNAs (DEmiRNAs) by comparing the expression levels observed in the CT and CN libraries. Furthermore, through DS, 9685 and 202 potential target transcripts were characterized as target genes for 268 known and 33 novel miRNAs, respectively. It was further predicted that a total of 264 targeted genes for the 85 DEmiRNAs are involved in proteoglycans in cancer and the AMP-activated protein kinase signaling pathway. After systemic analysis of prognosis-related miRNA targets in those cancer-related signal pathways, we found that two targets ezrin (EZR) and hematopoietic cell-specific Lyn substrate 1 (HCLS1) had the potential prognostic characteristics with CRC regarding over survival (OS) or recurrence. CONCLUSION In total, we found that endonucleolytic miRNA-directed mRNA cleavage occurs in CRC. A number of potential genes targeted by CRC-related miRNAs were identified and some may have the potential as prognosis markers of CRC. The present findings may lead to an improved better appreciation of the novel interaction mode between miRNAs and target genes in CRC.

中文翻译：

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大肠癌中microRNA及其核糖内切的靶mRNA的鉴定。

背景技术结直肠癌（CRC）在全球最常见的恶性肿瘤中排名第三。众所周知，微RNA（miRNA）在使mRNA不稳定并抑制其在该疾病中的翻译中起着至关重要的作用。但是，miRNA诱导的mRNA切割的机制尚待研究。方法在本研究中，高通量小RNA（sRNA）测序用于鉴定和分析来自六对结直肠癌组织（CT）和邻近组织（CN）的miRNA。降解组测序（DS）用于检测切割的靶基因。使用注释，可视化和集成发现数据库（DAVID）进行GO（基因本体论）和KEGG（京都基因与基因组百科全书）途径分析。结果总计 在CT和CN文库中分别鉴定了1278个已知的miRNA（分为337个家族）和131个新的miRNA。通过比较CT和CN文库中观察到的表达水平，将其中的420种已知miRNA和8种新颖miRNA定义为差异表达的miRNA（DEmiRNA）。此外，通过DS，将9685和202个潜在的目标转录本分别表征为268种已知miRNA和33种新颖miRNA的靶基因。进一步预测，针对癌症的蛋白聚糖和AMP激活的蛋白激酶信号通路，总共涉及85个DEmiRNA的264个靶向基因。在对与癌症相关的信号通路中与预后相关的miRNA目标进行系统分析后，我们发现两个靶点ezrin（EZR）和造血细胞特异的Lyn底物1（HCLS1）具有CRC关于超生存（OS）或复发的潜在预后特征。结论总的来说，我们发现内切miRNA定向的mRNA切割发生在CRC中。CRC相关的miRNA靶向了许多潜在基因，其中一些可能具有CRC预后的潜力。目前的发现可能导致对miRNA和CRC中靶基因之间新的相互作用模式的更好的了解。