The p53-signaling pathway and colorectal cancer: Interactions between downstream p53 target genes and miRNAs |
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| Authors: | Martha L Slattery Lila E Mullany Roger K Wolff Lori C Sakoda Wade S Samowitz Jennifer S Herrick |
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| Institution: | 1. Department of Medicine, University of Utah, 383 Colorow, Salt Lake City, UT, United States;2. Division of Research, Kaiser Permanente Northern California, Oakland, CA, United States;3. Department of Pathology, University of Utah, Salt Lake City, UT, United States |
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| Abstract: | IntroductionWe examined expression of genes in the p53-signaling pathway. We determine if genes that have significantly different expression in carcinoma tissue compared to normal mucosa also have significantly differentially expressed miRNAs. We utilize a sample of 217 CRC cases.MethodsWe focused on fold change (FC) > 1.50 or <0.67 for genes and miRNAs, that were statistically significant after adjustment for multiple comparisons. We evaluated the linear association between the differential expression of miRNA and mRNA. miRNA:mRNA seed-region matches also were determined.ResultsEleven dysregulated genes were associated with 37 dysregulated miRNAs; all were down-stream from the TP53 gene. MiR-150-5p (HR = 0.82) and miR-196b-5p (HR 0.73) significantly reduced the likelihood of dying from CRC when miRNA expression increased in rectal tumors.ConclusionsOur data suggest that activation of p53 from cellular stress, could target downstream genes that in turn could influence cell cycle arrest, apoptosis, and angiogenesis through mRNA:miRNA interactions. |
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