Molecular alterations that occur in cancer have the potential to be considered as either cancer biomarkers or targeted therapies or even both. In the presented study, we aimed to elucidate the gene regulatory network of metastatic colorectal cancer using data acquired from microarrays to reach the most common DEGs in colorectal cancer metastasis and find their possible regulatory mechanism by DETFs and DEmiRs. In this regards, seven microarray datasets were employed to assess the most important DEGs, DETFs and DEmiRs in colorectal cancer metastasis. Afterward, GRN based on DETFs and DEmiRs were constructed. Also ARACNE algorithm was used to construct an accurate GRN. GRN was analyzed structurally and then, two DETFs (LEF1 and ETV4) and a less-well known DEG (FABP6) by real time qRT-PCR in 50 patients with colorectal cancer were quantified. The constructed GRN highlighted the importance of some DETFs and DEmiRs in colorectal cancer metastasis. Interestingly the gene expression analysis by qRT-PCR on three candidate genes (LEF1, ETV4 and FABP6) indicated that the three genes were co-expressed in tumor samples, and were significantly associated with metastasis in colorectal cancer. Therefore, our experimental results proved a part of our comprehensive data analysis and system biology results. In summary, according to our empirical study we found the importance of three candidate genes as the potent prognostic factors in colorectal cancer metastasis. Also our study in a holistic insight on gene regulatory mechanism revealed the importance of some gene regulatory factors (DETFs and DEmiRs) and their potential as prognostic factors and/or targets in molecular targeted therapies in colorectal cancer.
Keywords: Colorectal cancer metastasis; DETFs; DEmiRs; ETV4; FABP6; GRN; Hippo signaling pathway; LEF1; Prognosis; Target therapy; Wnt signaling pathway.
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