P. F. Fedatto, Thais Inácio de Carvalho, J. C. Oliveira, D. Antônio, J. Pezuk, D. Tirapelli, O. Féres, J. J. Rocha, C. Scrideli, L. Tone, M. Brassesco
{"title":"MiR-708-5p as a Predictive Marker of Colorectal Cancer Prognosis","authors":"P. F. Fedatto, Thais Inácio de Carvalho, J. C. Oliveira, D. Antônio, J. Pezuk, D. Tirapelli, O. Féres, J. J. Rocha, C. Scrideli, L. Tone, M. Brassesco","doi":"10.6000/1927-7229.2016.05.01.2","DOIUrl":null,"url":null,"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.","PeriodicalId":14957,"journal":{"name":"Journal of Analytical Oncology","volume":"15 1","pages":"14-23"},"PeriodicalIF":0.0000,"publicationDate":"2016-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"3","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Analytical Oncology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.6000/1927-7229.2016.05.01.2","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 3
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.