MiR-708-5p as a Predictive Marker of Colorectal Cancer Prognosis
Pages 14-23
Paola Fernanda Fedatto, Thais Inácio de Carvalho, Jaqueline Carvalho de Oliveira, David Santos Marco Antônio, Julia Alejandra Pezuk, Daniela Pretti da Cunha Tirapelli, Omar Féres, José Joaquim Ribeiro da Rocha, Carlos Alberto Scrideli, Luiz Gonzaga Tone and María Sol Brassesco

DOI: http://dx.doi.org/10.6000/1927-7229.2016.05.01.2
Published: 05 April 2016

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.