miRNA Expression in Colon Polyps Provides Evidence for a Multihit Model of Colon Cancer

Changes in miRNA expression are a common feature in colon cancer. Those changes occurring in the transition from normal to adenoma and from adenoma to carcinoma, however, have not been well defined. Additionally, miRNA changes among tumor subgroups of colon cancer have also not been adequately evaluated. In this study, we examined the global miRNA expression in 315 samples that included 52 normal colonic mucosa, 41 tubulovillous adenomas, 158 adenocarcinomas with proficient DNA mismatch repair (pMMR) selected for stage and age of onset, and 64 adenocarcinomas with defective DNA mismatch repair (dMMR) selected for sporadic (n = 53) and inherited colon cancer (n = 11). Sporadic dMMR tumors all had MLH1 inactivation due to promoter hypermethylation. Unsupervised PCA and cluster analysis demonstrated that normal colon tissue, adenomas, pMMR carcinomas and dMMR carcinomas were all clearly discernable. The majority of miRNAs that were differentially expressed between normal and polyp were also differentially expressed with a similar magnitude in the comparison of normal to both the pMMR and dMMR tumor groups, suggesting a stepwise progression for transformation from normal colon to carcinoma. Among the miRNAs demonstrating the largest fold up- or down-regulated changes (≥4), four novel (miR-31, miR-1, miR-9 and miR-99a) and two previously reported (miR-137 and miR-135b) miRNAs were identified in the normal/adenoma comparison. All but one of these (miR-99a) demonstrated similar expression differences in the two normal/carcinoma comparisons, suggesting that these early tumor changes are important in both the pMMR- and dMMR-derived cancers. The comparison between pMMR and dMMR tumors identified four miRNAs (miR-31, miR-552, miR-592 and miR-224) with statistically significant expression differences (≥2-fold change)

A transcriptomal analysis of bovine oviductal epithelial cells collected during the follicular phase versus the luteal phase of the estrous cycle

BACKGROUND: Reproductive success depends on a functional oviduct for gamete storage, maturation, fertilization, and early embryonic development. The ovarian-derived steroids estrogen and progesterone are key regulators of oviductal function. The objective of this study was to investigate luteal and follicular phase-specific oviductal epithelial cell function by using microarray-based transcriptional profiling, to increase our understanding of mRNAs regulating epithelial cell processes, and to identify novel genes and biochemical pathways that may be found to affect fertility in the future. METHODS: Six normally cycling Angus heifers were assigned to either luteal phase (LP, n = 3) or follicular phase (FP, n = 3) treatment groups. Heifers in the LP group were killed between day 11 and 12 after estrus. Heifers in the FP group were treated with 25 mg PGF(2α) (Lutalyse, Pfizer, NY) at 8 pm on day 6 after estrus and killed 36 h later. Transcriptional profiling by microarray and confirmation of selected mRNAs by real-time RT-PCR analyses was performed using total RNA from epithelial cells isolated from sections of the ampulla and isthmus collected from LP and FP treatment groups. Differentially expressed genes were subjected to gene ontology classification and bioinformatic pathway analyses. RESULTS: Statistical one-way ANOVA using Benjamini-hochberg multiple testing correction for false discovery rate (FDR) and pairwise comparison of epithelial cells in the ampulla of FP versus LP groups revealed 972 and 597 transcripts up- and down-regulated, respectively (P < 0.05). Within epithelial cells of the isthmus in FP versus LP groups, 946 and 817 transcripts were up- and down-regulated, respectively (P < 0.05). Up-regulated genes from both ampulla and isthmus were found to be largely involved in cholesterol biosynthesis and cell cycle pathways, while down-regulated genes were found in numerous inflammatory response pathways. CONCLUSIONS: Microarray-based transcriptional profiling revealed phase of the cycle-dependent changes in the expression of mRNA within the epithelium of the oviducts’ ampulla and isthmus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12958-015-0077-1) contains supplementary material, which is available to authorized users