Project description:Aging of the uterine endometrium is a critical factor that affects reproductive success, but the mechanisms associated with uterine aging are unclear. In this study, we conducted a qualitative examination of age-related changes in endometrial tissues and identified candidate genes as markers for uterine aging. Gene expression patterns were assessed by twice RNA sequencing of uteri tissues from wild type (WT) C57BL/6 mice. First experimental samples were obtained from 5, 8 and 60-75 (aged) week-old WT (n=2, each). Second experimental samples were obtained from 5, 8 and 79 (aged) week-old WT (n=5, each). Gene expression data obtained by RNA-sequencing were validated by real-time PCR. Genes expressing the pro-inflammatory cytokines Il17rb and chemokines Cxcl12 and Cxcl14 showed differential expression between a group, which was composed of 5-week-old WT and 8-week-old WT (young), and aged WT mice. Protein expression levels of the above genes and IL-8, which functions downstream of IL17RB, were analyzed by quantitative immunohistochemistry of healthy human endometrium tissue samples from patients in their 20?s and 40?s (10 cases each). In these secretory phase samples, 3,3?- diaminobenzidine (DAB) staining intensity of IL17RB, CXCL12 and CXCL14 for patients in their 40?s was significantly higher than that for patients in their 20?s, as detected by a Mann Whitney U test. These results suggest that these genes are candidate markers for endometrial aging and for prediction of age-related infertility, although confirmation of these findings is needed in larger studies involving fertile and infertile women.
Project description:RATIONALE: Identification of genes that may be associated with developing certain types of cancer may someday provide important information about a person’s risk of getting cancer.
PURPOSE: This clinical trial is studying to see if certain genes may be associated with cancer in patients with cancer of the breast, prostate, lung, or colon and siblings of these patients.
Project description:The identification of target genes at genome-wide association study (GWAS) loci is a major obstacle for GWAS follow-up. To identify candidate target genes at the 16 known endometrial cancer GWAS risk loci, we performed HiChIP chromatin looping analysis of endometrial cell lines. To enrich for enhancer-promoter interactions, a mechanism through which GWAS variation may target genes, we captured loops associated with H3K27Ac histone, characteristic of promoters and enhancers. Analysis of HiChIP loops contacting promoters revealed enrichment for endometrial cancer GWAS heritability and intersection with endometrial cancer risk variation identified 103 HiChIP target genes at 13 risk loci. Expression of four HiChIP target genes (SNX11, SRP14, HOXB2 and BCL11A) was associated with risk variation, providing further evidence for their regulation. Network analysis functionally prioritized a set of proteins that interact with those encoded by HiChIP target genes, and this set was enriched for pan-cancer and endometrial cancer drivers. Lastly, HiChIP target genes and prioritized interacting proteins were over-represented in pathways related to endometrial cancer development. In summary, we have generated the first global chromatin looping data from endometrial cells, enabling analysis of all known endometrial cancer risk loci and identifying biologically relevant candidate target genes.
Project description:The present study has focused on the identification of the differences between expression patterns of kinin-dependent genes in endometrial cancer
Project description:The present study has focused on the identification of the differences between expression patterns of kinin-dependent genes in endometrial cancer For microarray analysis 20 samples were used: 7 control samples, 3 - G1 samples, 8 - G2 samples and 2 - G3 samples.
Project description:The molecular events that mediate the epithelial to mesenchymal transition (EMT) in endometrial cancer remain poorly understood. Using cDNA microarrays, we analyzed a group of endometrial carcinosarcomas (ECS), a true example of EMT in vivo, and we compared their gene expression profiles with those obtained from a group of endometrioid endometrial carcinomas (EEC). The HMGA2 gene (High Mobility Group AT-hook 2), an embryonic nuclear factor that mediates EMT in various tumour models, was among the genes overexpressed in ECS, and HMGA2 overexpression was confirmed in 54% of ECSs by qRT-PCR and immunohistochemistry. Moreover, we found a significant inverse correlation between the expression of HMGA2 and let-7b, a member of the let-7 family of miRNAs that represses HMGA2 expression. These changes were also associated with overexpression of Lin28B, a suppressor of microRNA biogenesis implicated in cancer progression and metastasis. Finally, HMGA2 overexpression, which was detected in less than 3% of EECs, was observed in many non-endometrioid carcinomas (46%). For the first time, we describe a role for HMGA2 in both the process of EMT that contributes to endometrial carcinogenesis and in the acquisition of aggressive phenotypes by this neoplasia. Moreover, we demonstrate changes in the expression of genes modulating processes such as EMT, muscle differentiation, the expression of cancer testis antigens (CTAs) and the immune response. Identification of new molecular markers in endometrial carcinogenesis 15 endometrial carcinosarcomas and 23 endometrioid endometrial carcinoma