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

Abstract

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.

Keywords: bioinformatics; biomarker; colorectal cancer; dataset; microRNA.

Figure 1

Differentially expressed miRNAs between colorectal cancer samples and normal tissues in at least 3 of 10 datasets. logFC values are reported with red scale boxes for up-regulated miRNAs and blue scale boxes for the down-regulated miRNAs. lgFC values were divided in “highly” (logFC ≥ 3), “moderately” (logFC 1.5 <x< 3), “lightly” (logFC 0.5 <x< 1.5) and “poorly” (logFC 0 <x< 0.5) up-regulated or down-regulated (negative logFC values). ID Datasets boxes were colored in a different manner according to the different microarray platform adopted in the dataset.

Figure 2

mirDIP gene target analysis – Interaction between selected miRNAs and main altered genes in CRC. For each miRNA is reported the level of interaction with the 10 genes involved in CRC is reported. The intensity of interaction is highlighted with a color scale ranging from dark red (very high interaction) to yellow (low interaction).

Figure 3

Diana-mirPath pathway analysis – Interaction between selected miRNAs and TCGA colorectal cancer pathways. Prediction pathway analysis of the interaction between selected miRNAs and the main genes and pathways involved in CRC development according to The Cancer Genome Atlas Network. For each miRNA is indicated the number of targeted gene within a specific pathway is indicated by highlighting the corresponding box with a color scale ranging from red (40 genes targeted) to light red (0 genes targeted).

Figure 4

Diana-mirPath pathway analysis – Interaction between selected miRNAs and several molecular pathways involved in cancer development. Prediction pathway analysis of the interaction between individually selected miRNAs and the molecular and signaling pathways involved in CRC development. For each miRNA is indicated the number of targeted gene within a specific pathway by highlighting the corresponding box with a color scale ranging from red (80 genes targeted) to light red (0 genes targeted).