Colorectal cancer (CRC) is one of the most frequent cancers occurring in developed countries. Distant CRC metastasis causes more than 90% of CRC-associated mortality. MicroRNAs (miRNAs) play a key role in regulating tumor metastasis and could be potential diagnostic biomarkers in CRC patients. This study is aimed at identifying miRNAs that can be used as diagnostic biomarkers for CRC metastasis. Towards this goal, we compared the expression of five miRNAs commonly associated with metastasis (i.e., miR-10b, miR-200c, miR-155, miR-21, and miR-31) between primary CRC (pCRC) tissues and corresponding metastatic lymph nodes (mCRC). Further, bioinformatics analysis of miR-31 was performed to predict target genes and related signaling pathways. Results showed that miR-31, miR-21, miR-10b, and miR-155 expression was increased to different extents, while miR-200c expression was lower in mCRC than that in pCRC. Moreover, we found that the level of both miR-31 and miR-21 was notably increased in pCRC when lymph node metastasis (LNM) was present, and the increase of miR-31 expression was more profound. Hence, upregulated miR-31 and miR-21 expression might be a miRNA signature in CRC metastasis. Moreover, we detected a higher miR-31 level in the plasma of CRC patients with LNM compared to patients without LNM or healthy individuals. With the bioinformatics analysis of miR-31, 121 putative target genes and transition of mitotic cell cycle and Wnt signaling pathway were identified to possibly play a role in CRC progression. We next identified seven hub genes via module analysis; of these, TNS1 was most likely to be the target of miR-31 and had significant prognostic value for CRC patients. In conclusion, miR-31 is significantly increased in the cancer tissues and plasma of CRC patients with LNM; thus, a high level of miR-31 in the plasma is a potential biomarker for the diagnosis of LNM of CRC.

中文翻译：

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miR-31在结直肠癌淋巴结转移患者中的诊断价值调查和生物信息学分析。

大肠癌（CRC）是发达国家中最常见的癌症之一。远距离的CRC转移导致90％以上的CRC相关死亡率。MicroRNA（miRNA）在调节肿瘤转移中起关键作用，并且可能是CRC患者的潜在诊断生物标志物。这项研究旨在鉴定可用作CRC转移诊断生物标志物的miRNA。为了达到这个目标，我们比较了原发性CRC（pCRC）组织与相应转移淋巴结之间通常与转移相关的五个miRNA（即miR-10b，miR-200c，miR-155，miR-21和miR-31）的表达节点（mCRC）。此外，对miR-31进行生物信息学分析以预测目标基因和相关的信号通路。结果显示，miR-31，miR-21，miR-10b和miR-155的表达均有不同程度的增加，而miR-200c在mCRC中的表达低于在pCRC中的表达。此外，我们发现当存在淋巴结转移（LNM）时，pCRC中miR-31和miR-21的水平均显着增加，并且miR-31表达的增加更为深刻。因此，上调的miR-31和miR-21表达可能是CRC转移中的miRNA标志。此外，与没有LNM的患者或健康个体相比，我们在患有LNM的CRC患者的血浆中检测到更高的miR-31水平。通过对miR-31的生物信息学分析，确定了121个推定的靶基因以及有丝分裂细胞周期和Wnt信号通路的转变可能在CRC进程中起作用。接下来，我们通过模块分析确定了七个中心基因。其中，TNS1最有可能成为miR-31的靶标，并且对CRC患者具有重要的预后价值。总之，在患有LNM的CRC患者的癌组织和血浆中，miR-31显着增加。因此，血浆中高水平的miR-31是诊断CRC LNM的潜在生物标志物。