MiR-708-5p as a Predictive Marker of Colorectal Cancer Prognosis

Abstract

Background : MicroRNAs (miRNA) are short non-coding RNA that act as negative regulators of gene expression. Altered levels of miR-708-5p have recently been described in many tumors, although its contribution in colorectal cancer (CRC) pathophysiology remains unclear. Methods/Patients : Quantitative real-time polymerase chain reaction was employed to evaluate the expression of miR-708-5p in 50 CRC and 20 paired adjacent noncancerous tissues. The relationship between miRNA levels and clinicopathological features was estimated using the Mann-Whitney test, and survival curves calculated by the Kaplan-Meier method. Additionally, in vitro assays were performed to investigate the possible role of miR-708-5p on CRC cell survival. Results : The expression level of miR-708-5p was significantly decreased in CRC tissues (3.79 fold-change, p=0.0112) when compared with non-neoplastic colon samples. Paired analysis in 20 CRC samples with their corresponding adjacent non-neoplastic tissue showed miR-708 downregulation in 60% of them. The same pattern was seen in DLD1 and HT-29 cell lines (~50-fold decrease). Interestingly, higher expression is observed in patients with poor prognosis such as stage III/IV, relapse/metastasis and death, and shorter 5-year event free survival. Exogenous expression of miR-708 exerted a significant influence on clonogenicity in vitro . Conclusion : These results suggest that reduced miR-708-5p expression may contribute to the first stages of colorectal carcinogenesis. A shift in the regulation of miR-708-5p might operate in more severe stages of the disease. It seems that lower levels of miR-708 expression might connote less advanced disease and better prognosis. Further studies are needed to corroborate our results and better elucidate the role of miR-708 in CRC.