UTX is implicated in embryonic development and lineage specification. However, how this X-linked histone demethylase contributes to the occurrence and progression of breast cancer remains to be clarified. Here we report that UTX is physically associated with estrogen receptor (ER) and functions in ER-regulated transcription. We showed that UTX coordinates with JHDM1D and CBP to direct H3K27 methylation-acetylation transition and to create a permissive chromatin state on ER targets. Genome-wide analysis of the transcriptional targets of UTX by ChIP-seq identified a set of genes such as chemokine receptor CXCR4 that are intimately involved in breast cancer tumorigenesis and metastasis. We demonstrated that UTX promotes the proliferation and migration of ER breast cancer cells. Interestingly, UTX itself is transactivated by ER, forming a feed-forward loop in the regulation of hormone response. Indeed, UTX is upregulated during ER breast cancer progression, and the expression level of UTX is positively correlated with that of CXCR4 and negatively correlated with the overall survival of ER breast cancer patients. Our study identified a feed-forward loop between UTX and ER in the regulation of hormonally responsive breast carcinogenesis, supporting the pursuit of UTX as an emerging therapeutic target for the intervention of certain ER breast cancer with specific epigenetic vulnerability.
Compared with diet alone or no diet, 50-100 g/day ONOG supplement to structured dietary intervention, at a dose of 100 g/day especially, contributes to the Type 2 DM patients meeting MetS criteria in their metabolic control and CVD risk prevention, with external factors being controlled.
One population from each of six plant species along both sides of the Juyong-guan Great Wall, together with one population from each of five species along both sides of a path on a mountain top near Juyong-guan, were selected to study the effect of the Great Wall as a barrier on genetic differentiation between two subpopulations using RAPD markers. Significant genetic differentiation was found between the subpopulations on both sides of the Great Wall. A wind-pollinated woody species, Ulmus pumila, showed less genetic differentiation than four insect-pollinated species: Prunus armeniaca, Ziziphus jujuba, Vitex negundo, and Heteropappus hispidus. Cleistogenes caespitosa, a windpollinated perennial herb, displayed more genetic differentiation between subpopulations than the insect-pollinated species because of its propagation strategy. Although AMOVA analysis showed that subpopulations divided by a mountain path had diverged genetically, the variance component between the subpopulations on both sides of the Great Wall was significantly larger than that between the subpopulations at the control site. Therefore, it is reasonable to deduce that the Juyong-guan Great Wall has served as a physical barrier to gene flow between subpopulations separated for more than 600 years.
Overexpression of Id-1 is a novel marker for advanced RCC which is positively correlated with EGFR expression. Our results suggest that Id-1 may play an important role in the development of RCC and indicate that Id-1 is a potential marker of patients with a poor prognosis.
We present the most comprehensive catalogue of cancer-associated gene alterations through characterization of tumor transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes project. Using matched whole-genome sequencing data, we attributed RNA alterations to germline and somatic DNA alterations, revealing likely genetic mechanisms. We identified 444 associations of gene expression with somatic non-coding single-nucleotide variants. We found 1,872 splicing alterations associated with somatic mutation in intronic regions, including novel exonization events associated with Alu elements. Somatic copy number alterations were the major driver of total gene and allele-specific expression (ASE) variation. Additionally, 82% of gene fusions had structural variant support, including 75 of a novel class called “bridged” fusions, in which a third genomic location bridged two different genes. Globally, we observe transcriptomic alteration signatures that differ between cancer types and have associations with DNA mutational signatures. Given this unique dataset of RNA alterations, we also identified 1,012 genes significantly altered through both DNA and RNA mechanisms. Our study represents an extensive catalog of RNA alterations and reveals new insights into the heterogeneous molecular mechanisms of cancer gene alterations.
Trigeminal schwannoma of the mandible can develop to involve intracranial extension. Radiological identification of an expanded foramen ovale may facilitate pre-operative identification.
Immune reactions in the tumor micro-environment are one of the cancer hallmarks and emerging immune therapies have been proven effective in many types of cancer. To investigate cancer genomeimmune interactions and the role of immuno-editing or immune escape mechanisms in cancer development, we analyzed 2,834 whole genomes and RNA-seq datasets across 31 distinct tumor types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) project with respect to key immunogenomic aspects. We show that selective copy number changes in immune-related genes could contribute to immune escape. Furthermore, we developed an index of the immuno-editing history of each tumor sample based on the information of mutations in exonic regions and pseudogenes. Our immuno-genomic analyses of pan-cancer analyses have the potential to identify a subset of tumors with immunogenicity and diverse background or intrinsic pathways associated with their immune status and immuno-editing history.All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
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