MiR-29c downregulation contributes to metastatic progression in colorectal cancer

Abstract

We have read with interest the recent article by Zhang et al. [1], which provides novel exciting findings about the role of miR29c in colorectal cancer (CRC) progression and metastasis. Although little is known about the significance of this microRNA in CRC, some previous studies suggest its potential tumor suppressor role in this disease. Thus, miR-29c has been reported to be expressed at low levels in CRC [2, 3] and also to be predictive of CRC early recurrence [3]. In concordance with these data, the authors found that miR-29c was markedly downregulated in primary CRC tissues from patients with distant metastasis, and predicted worse outcome. Interestingly, miR-29c showed higher expression in liver metastatic tissues in comparison with primary tumor specimens. This observation suggests that miR29c downregulation could be a transient relevant event in CRC progression to metastatic disease. Moreover, miR-29c reduced epithelial-to-mesenchymal transition, cell migration and invasion abilities of CRC cells, and metastasis development in vivo, further supporting its role in CRC metastatic development [1]. However, the precise status of miR-29c in metastatic CRC tissues is a major question to be fully investigated. Thus, we quantified miR-29c in primary and paired metastatic tissues from 17 CRC patients, 12 with liver metastasis and 5 with lung metastasis, using Taqman Low Density Arrays (TLDAs) panel A (Applied Biosystems). A pathologist reviewed the specimens to further confirm the diagnosis. All samples were taken anonymously and the ethical committee and institutional review board approved the project. Relative gene expression analysis was carried out using the 2 method and U6B as internal control. We observed similar miR-29c expression between primary and metastatic tissues from those 12 CRC patients with liver metastasis. However, almost threefold increased miR-29c levels were found in the metastatic tissues of those cases with lung metastasis. We then investigated whether these differences were due to expression changes in the primary tissues or dependent on the metastatic site. Interestingly, miR-29c showed significantly lower expression in primary CRC tissues from patients with lung metastasis compared with those cases with liver metastasis (P = 0.046). No differences were observed when comparing miR-29c between liver and lung CRC metastatic tissues (P = 0.934). In summary, our results would indicate that deeper miR-29c downregulation would be required in the premetastatic CRC cell to develop lung metastasis than liver metastasis. In addition, the potential predictive value of miR-29c determining the CRC metastatic niche should be further confirmed in forthcoming studies.