Research Article: Integrated analysis of colorectal cancer microRNA datasets: identification of microRNAs associated with tumor development

Date Published: May 18, 2018

Publisher: Impact Journals

Author(s): Luca Falzone, Letizia Scola, Antonino Zanghì, Antonio Biondi, Antonio Di Cataldo, Massimo Libra, Saverio Candido.


Colorectal cancer (CRC) is one of the leading cause of cancer death worldwide. Currently, no effective early diagnostic biomarkers are available for colorectal carcinoma. Therefore, there is a need to discover new molecules able to identify pre-cancerous lesions. Recently, microRNAs (miRNAs) have been associated with the onset of specific pathologies, thus the identification of miRNAs associated to colorectal cancer may be used to detect this pathology at early stages. On these bases, the expression levels of miRNAs were analyzed to compare the miRNAs expression levels of colorectal cancer samples and normal tissues in several miRNA datasets. This analysis revealed a group of 19 differentially expressed miRNAs. To establish the interaction between miRNAs and the most altered genes in CRC, the mirDIP gene target analysis was performed in such group of 19 differentially expressed miRNAs. To recognize miRNAs able to activate or inhibit genes and pathways involved in colorectal cancer development DIANA-mirPath prediction analysis was applied. Overall, these analyses showed that the up-regulated hsa-miR-183-5p and hsa-miR-21-5p, and the down-regulated hsa-miR-195-5p and hsa-miR-497-5p were directly related to colorectal cancer through the interaction with the Mismatch Repair pathway and Wnt, RAS, MAPK, PI3K, TGF-β and p53 signaling pathways involved in cancer development.

Partial Text

Colorectal carcinoma (CRC) is the most frequent tumor affecting the entire digestive tract. According to the data reported by GLOBOCAN 2012, CRC is the second most frequent cancer in women and the third most frequent in males. Overall, it is the fourth most frequent cancer in both sexes preceded only by breast, prostate and lung cancers. This tumor is usually diagnosed at the average age of 69 years, in which 60% are over the age of 65 and 36% are over 75 years. Although many therapeutic approaches for CRC are available today, this pathology is still responsible for a high number of deaths, representing the fourth cause of mortality due to cancer diseases (693.933 deaths, 8.5% of all tumor deaths in 2012) [1,2]. Over the years, the geographical distribution of CRC has changed, showing today a higher incidence and mortality rates mainly in the more developed countries (Australia/New Zealand/Europe) and in the less developed areas (Eastern Europe/Russia/South America) respectively [3]. Despite the epidemiological data described above, CRC mortality rate is declining in many developed countries worldwide thanks to the improvement of anti-neoplastic treatments and the new screening programs adopted [4].

Recently, a growing body of evidence indicated the improvement of therapeutic strategies for colorectal carcinoma [32,33]. However, such improvement was not observed regarding screening and diagnostic approaches [34,35]. Conflicting data were obtained for the identification of sensitive molecular biomarkers in the context of early diagnosis [36], while promising results derived from the analysis of miRNAs.




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