Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Whole-genome analysis approaches are identifying recurrent cancer-associated somatic alterations in noncoding DNA regions. We combined somatic copy number analysis of 12 tumor types with tissue-specific epigenetic profiling to identify significant regions of focal amplification harboring super-enhancers. Copy number gains of noncoding regions harboring super-enhancers near KLF5, USP12, PARD6B and MYC are associated with overexpression of these cancer-related genes. We show that two distinct focal amplifications of super-enhancers 3' to MYC in lung adenocarcinoma (MYC-LASE) and endometrial carcinoma (MYC-ECSE) are physically associated with the MYC promoter and correlate with MYC overexpression. CRISPR/Cas9-mediated repression or deletion of a constituent enhancer within the MYC-LASE region led to significant reductions in the expression of MYC and its target genes and to the impairment of anchorage-independent and clonogenic growth, consistent with an oncogenic function. Our results suggest that genomic amplification of super-enhancers represents a common mechanism to activate cancer driver genes in multiple cancer types.
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PMID:Identification of focally amplified lineage-specific super-enhancers in human epithelial cancers. 2665 44

We conducted a meta-analysis of three endometrial cancer genome-wide association studies (GWAS) and two follow-up phases totaling 7,737 endometrial cancer cases and 37,144 controls of European ancestry. Genome-wide imputation and meta-analysis identified five new risk loci of genome-wide significance at likely regulatory regions on chromosomes 13q22.1 (rs11841589, near KLF5), 6q22.31 (rs13328298, in LOC643623 and near HEY2 and NCOA7), 8q24.21 (rs4733613, telomeric to MYC), 15q15.1 (rs937213, in EIF2AK4, near BMF) and 14q32.33 (rs2498796, in AKT1, near SIVA1). We also found a second independent 8q24.21 signal (rs17232730). Functional studies of the 13q22.1 locus showed that rs9600103 (pairwise r(2) = 0.98 with rs11841589) is located in a region of active chromatin that interacts with the KLF5 promoter region. The rs9600103[T] allele that is protective in endometrial cancer suppressed gene expression in vitro, suggesting that regulation of the expression of KLF5, a gene linked to uterine development, is implicated in tumorigenesis. These findings provide enhanced insight into the genetic and biological basis of endometrial cancer.
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PMID:Five endometrial cancer risk loci identified through genome-wide association analysis. 2713 1

Objective: Long noncoding RNA urothelial carcinoma associated 1 (UCA1) was found to facilitate endometrial cancer cell metastasis, and high UCA1 expression predicted endometrial cancer development and patients' worsened outcomes. This research aimed to investigate the cancer promoting role and mechanism of UCA1 in endometrial cancer. Materials and Methods: Around 64 endometrioid adenocarcinoma patients' tissue specimens were analyzed by qRT-PCR. Primary endometrial cancer cell culture was established in vitro. UCA1 overexpression or knockdown was executed by adenoviral transduction. Cell proliferation, apoptosis, colony formation, transwell invasion, and epithelia-to-mesenchymal transition of primary endometrial cancer cells were assessed. Interactions among UCA1, microRNAs (miRNAs), and mRNAs were investigated by luciferase reporter assay and argonaute 2 (AGO2)-RNA immunoprecipitation. Nude mouse xenograft assay was used to explore the role of UCA1 in endometrial cancer in vivo. Results: UCA1 was significantly upregulated in endometrial cancer tissues compared to normal tissues. High expression of UCA1 associated with endometrial cancer progression and patients' decreased survival. Overexpressing UCA1 significantly increased the malignancy of primary endometrial cancer cells in vitro, while UCA1 knockdown showed opposite effect. Kruppel-like factor 5 (KLF5) and relaxin like family peptide receptor 1 (RXFP1) were found as two UCA1 co-expressing genes in endometrial cancer. UCA1 increased the malignancy of endometrial cells partially through KLF5, and it increased the relaxin 2-induced endometrial cancer cell metastasis through RXFP1. UCA1 reduced the si-RNA-induced silencing of KLF5 and RXFP1 genes in endometrial cancer cells. MiR-143-3p and miR-1-3p were found to interact with both UCA1 and KLF5 mRNA. In addition, knockdown of UCA1 suppressed tumor growth in endometrial cancer in vivo. Conclusion: UCA1 might facilitate endometrial cancer development by upregulating KLF5 and RXFP1 gene expression by sponging miR-143-3p and miR-1-3p.
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PMID:Long Noncoding RNA UCA1 Facilitates Endometrial Cancer Development by Regulating KLF5 and RXFP1 Gene Expressions. 3241 93