Downregulation of miR-214 is specific of liver metastasis in colorectal cancer and could play a role determining the metastatic niche.

Abstract

To the Editor: MicroRNAs are small, non-coding RNAs that negatively regulate the expression of their target genes. Aberrant microRNA expression levels have been largely reported in human cancer and have emerged as novel candidates for targeted therapies. It has been recently reported that miR214 is a negative regulator of colorectal cancer (CRC) liver metastasis. Interestingly, the authors found that restored miR214 expression suppressed in vitro proliferation, migration and invasion, and tumor growth and liver metastasis in vivo, and identified FGFR1 as a miR-214 target. However, the fact that it does not clarify whether miR-214 downregulation is a molecular event specific of liver metastases or characteristic of the metastatic CRC with independence of the metastatic site is a relevant question to be addressed. This prompted us to analyzed the expression pattern of 377 mature microRNAs using Taqman low-density arrays (TLDAs) panel A (Applied Biosystems) in 17 CRC patients, 12 with liver metastasis, and 5 with lungmetastasis previously reviewed by a pathologist (F.R.) to further confirm the diagnosis. All samples were taken anonymously, and the ethical committee and institutional review board approved the project. Analysis of relative gene expression data was performed using the 2T method, and U6B was used as internal control. Thus, we found miR-214 significantly downregulated in liver metastatic tissues compared with their paired primary CRC tissues (P=0.007). Moreover, we detected higher miR214 levels in lung metastasis compared to their paired primary CRC tissues, although significance was not achieved in this case (P=0.092) and no differences were observed in miR-214 expression between the liver and lung metastatic CRC tissues (P=0.282). Interestingly, miR-214 showed significantly lower expression in primary CRC tissues from patients with lung metastasis than in those with liver metastasis (P=0.024). Altogether, our results confirm the previous reported role of miR-214 in CRC with liver metastasis and additionally indicate that miR-214 downregulation is specific of liver metastatic location. Moreover, our observations suggest that miR-214 expression in the primary CRC could be playing a potential role determining the metastatic niche although further studies are needed to clarify this point.