Although microRNAs (miRNA) are involved in all hallmarks of cancer, miRNA dysregulation in metastasis remains poorly understood and contradictory results have been published. The aim of this work was to identify miRNAs associated with metastatic progression of colorectal cancer (CRC). Novel and previously published next generation sequencing (NGS) datasets generated from 268 samples with primary (pCRC) and metastatic CRC (mCRC; liver, lung and peritoneal metastases) and tumor adjacent tissues were analyzed. Differential expression analysis was performed using a meticulous bioinformatics pipeline, including only bona fide miRNAs, utilizing miRNA-tailored quality control and processing, and applying a physiologically meaningful cut-off value (100 reads per million). The results were adjusted for host tissue background expression and samples from the different metastatic sites were independently analyzed. A metastatic signature containing five miRNAs up-regulated at multiple metastatic sites was identified (Mir-210_3p, Mir-191_5p, Mir-8-P1b_3p (mir-141-3p), Mir-1307_5p, and Mir-155_5p) along with a number of miRNAs that were differentially expressed at individual metastatic sites. Several of these have previously been implicated in metastasis through involvement in epithelial-to-mesenchymal transition and hypoxia, while other identified miRNAs represent novel findings. The identified differentially expressed miRNAs confirm known associations and contribute novel insights into miRNA involvement in the metastatic process. The use of open science practices facilitates reproducibility, and new datasets may easily be added to the publicly available pipeline to continuously improve the knowledge in the field. The identified set of miRNAs provides a reliable starting-point for further research into the role of miRNAs in metastatic progression.

中文翻译：

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转移性结直肠癌的 microRNA 特征

尽管 microRNA (miRNA) 涉及癌症的所有标志，但转移中的 miRNA 失调仍然知之甚少，并且已经发表了相互矛盾的结果。这项工作的目的是鉴定与结直肠癌 (CRC) 转移进展相关的 miRNA。分析了从 268 个具有原发性 (pCRC) 和转移性 CRC (mCRC；肝、肺和腹膜转移) 和肿瘤邻近组织的样本生成的新的和以前发表的下一代测序 (NGS) 数据集。差异表达分析是使用细致的生物信息学管道进行的，仅包括真正的 miRNA，利用 miRNA 定制的质量控制和处理，并应用具有生理意义的截止值（每百万读数 100）。结果针对宿主组织背景表达进行了调整，并且对来自不同转移部位的样本进行了独立分析。鉴定了包含在多个转移位点上调的五个 miRNA 的转移特征（Mir-210_3p、Mir-191_5p、Mir-8-P1b_3p(mir-141-3p)、Mir-1307_5p 和 Mir-155_5p) 以及许多在单个转移位点差异表达的 miRNA。其中一些先前已通过参与上皮间质转化和缺氧而与转移有关，而其他已鉴定的 miRNA 代表了新的发现。鉴定出的差异表达的 miRNA 证实了已知的关联，并为 miRNA 参与转移过程提供了新的见解。开放科学实践的使用促进了可重复性，并且可以轻松地将新数据集添加到公开可用的管道中，以不断改进该领域的知识。确定的 miRNA 集为进一步研究 miRNA 在转移进展中的作用提供了可靠的起点。