Identification of Unique miRNA Biomarkers in Colorectal Adenoma and Carcinoma Using Microarray: Evaluation of Their Putative Role in Disease Progression
MicroRNAs (miRNAs) are known to be dysregulated and play a key role in cancer progression. The present study aims to identify the miRNAs associated with colorectal adenoma and carcinoma to evaluate their role in tumor progression and metastasis using microarray. In silico analysis of miRNAs was performed on five different microarray data sets that represented the genes and miRNAs expressed in colorectal adenoma and carcinoma. We identified 10 different miRNAs that were common to both colorectal adenoma and carcinoma, namely, miR9, miR96, miR135b, miR137, miR147, miR182, miR183, miR196b, miR224, and miR503. Of these, miR135b and miR147 were significantly downregulated in colorectal adenoma but upregulated in carcinoma. In addition, we studied the gene expression profile associated with colorectal adenocarcinoma and identified three genes, namely, ZBED3, SLC10A3, and FOXQ1, that were significantly downregulated in colorectal adenoma compared to carcinoma. Interestingly, of all the miRNAs and genes associated with colorectal adenocarcinoma, the myoglobin (MB) gene was identified to be under the direct influence of miR135b, showing an inverse relationship between them in adenoma and carcinoma. Most of the identified miRNAs and associated genes are involved in signaling pathways of cell proliferation, angiogenesis, and metastasis. The present study has identified putative miRNA targets and their associated gene networks which could be used as potential biomarkers of colon adenocarcinoma. Moreover, the association of miR135b and MB gene is very unique and can be considered as a lead candidate for novel cancer therapeutics. 1. Introduction Colorectal cancer is one of the most common gastrointestinal cancers that shows a rising trend due to the dietary habits and lifestyle modifications. Accumulation of genetic and epigenetic aberrations predisposes the colonic epithelium to undergo gradual transformation with loss of cellular architecture and initiation of a benign adenoma, which subsequently develops into a malignant adenocarcinoma [1]. Successful screening methods have enabled early detection and hence reduction in the mortality rate associated with colorectal adenocarcinoma [2]. In addition to the oncogenes and the tumor suppressor genes involved in cancer initiation and progression, many other small molecules such as the oncoproteins, antisense RNAs, and microRNAs (miRNAs) are also implicated in cancer and its signaling mechanisms [3]. Among the small molecules involved in cancer progression and metastasis, the microRNAs (miRNAs) which are 21–25
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