Dysregulation of Synaptic Signaling Genes Is Involved in Biology of Uterine Leiomyoma
| Autor: | Igor But, Maja Pakiž, Jovan Krsteski, Uroš Potočnik, Mario Gorenjak |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Adult NPTX1 Computational biology Biology QH426-470 CACNA1A Article 03 medical and health sciences 0302 clinical medicine Genetics Humans Epigenetics NPTX2 DRD2 Enhancer Promoter Regions Genetic Gene Genetics (clinical) Uterine leiomyoma Leiomyoma Sequence Analysis RNA Myometrium Promoter CHRM2 uterine leiomyomas Middle Aged female genital diseases and pregnancy complications 030104 developmental biology Synapses Uterine Neoplasms Female Synaptic signaling Hypersensitive site 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Genes, Vol 12, Iss 1179, p 1179 (2021) Genes Volume 12 Issue 8 |
| ISSN: | 2073-4425 |
| Popis: | Uterine leiomyomas are tumors, which are hormone driven and originate from the smooth muscle layer of the uterine wall. In addition to known genes in leiomyoma pathogenesis, recent approaches also highlight epigenetic malfunctions as an important mechanism of gene dysregulation. RNA sequencing raw data from pair-matched normal myometrium and fibroid tumors from two independent studies were used as discovery and validation sets and reanalyzed. RNA extracted from normal myometrium and fibroid tumors from 58 Slovenian patients was used as independent confirmation of most significant differentially expressed genes. Subsequently, GWA data from leiomyoma patients were used in order to identify genetic variants at epigenetic marks. Gene Ontology analysis of the overlap of two independent RNA-seq analyses showed that NPTX1, NPTX2, CHRM2, DRD2 and CACNA1A were listed as significant for several enriched GO terms. All five genes were subsequently confirmed in the independent Slovenian cohort. Additional integration and functional analysis showed that genetic variants in these five gene regions are listed at a chromatin structure and state, predicting promoters, enhancers, DNase hypersensitivity and altered transcription factor binding sites. We identified a unique subgroup of dysregulated synaptic signaling genes involved in the biology and pathogenesis of leiomyomas, adding to the complexity of tumor biology. |
| Databáze: | OpenAIRE |
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