The progesterone receptor (PR) modulates estrogen receptors α (ERα) action in breast cancer; it is an upregulated target gene of ER, and its expression is dependent on estrogen. PR is also a valuable prognostic biomarker in breast cancer, especially in hormone-positive breast cancer. High expression of PR is more frequently observed in tumors with a better baseline prognosis (ie, luminal A) than tumors with a poor baseline prognosis (ie, luminal B). In the following review, we present the role of PR in breast cancer, including the genomic characteristics and pathways in breast cancer, PR and endocrine therapy.
Neural Cellular Automata (NCAs) have been proven effective in simulating morphogenetic processes, the continuous construction of complex structures from very few starting cells. Recent developments in NCAs lie in the 2D domain, namely reconstructing target images from a single pixel or infinitely growing 2D textures. In this work, we propose an extension of NCAs to 3D, utilizing 3D convolutions in the proposed neural network architecture. Minecraft is selected as the environment for our automaton since it allows the generation of both static structures and moving machines. We show that despite their simplicity, NCAs are capable of growing complex entities such as castles, apartment blocks, and trees, some of which are composed of over 3,000 blocks. Additionally, when trained for regeneration, the system is able to regrow parts of simple functional machines, significantly expanding the capabilities of simulated morphogenetic systems.
Purpose
To investigate the role of N6-methyladenosine (m6A) RNA modification in the pathogenesis of Graves' ophthalmopathy (GO).
Methods
Surgically excised extraocular muscles from 7 patients with GO and 5 subjects without GO were used. The global m6A levels in the specimens were determined using an m6A RNA methylation quantification kit. RNA sequencing (RNA-seq) was used to analyze the molecules involved in the regulation of m6A RNA methylation and the differential expression of mRNAs between the two groups (4 eyes, respectively). The expression of m6A RNA modification genes was evaluated by real-time PCR. The functional implications of the gene alterations between the GO and control specimens were determined by Gene Ontology analysis.
Results
The m6A level was significantly increased in the specimens of GO patients compared to the control specimens (P < 0.05). The expression of m6A methylation regulators, such as WT1 associated protein (WTAP), alkylation repair homolog protein 5 (ALKBH5), E74 like ETS transcription factor 3 (ELF3), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), YTHDF3 and YTH domain containing 2 (YTHDC2), was significantly upregulated (P < 0.05). Gene Ontology enrichment analysis showed that the most highly upregulated genes and biological pathways were related to the immune response and inflammatory processes such as lymphocyte activation, leukocyte differentiation, cytokine production and cytokine-mediated signaling pathways.
Conclusions
Our results suggest that m6A methylation may play a critical role in the pathogenesis of GO and that targeting genes that regulate m6A methylation may provide a new therapeutic approach for GO.
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