Dataset Information

SATB2 and NGR1: potential upstream regulatory factors in uterine leiomyomas.

ABSTRACT: PURPOSE:We attempted to identify the genes involved in the pathogenesis of uterine leiomyomas, under a hypothesis that the aberrant expression of upstream regulatory genes caused by aberrant DNA methylation is involved in the onset and development of uterine leiomyomas. METHODS:To find such genes, we compared genome-wide mRNA expression and DNA methylation in uterine leiomyomas and adjacent normal myometrium. Analysis of the data by Ingenuity Pathway Analysis software identified SATB2 which is known to be an epigenetic regulator, and NRG1 as candidate upstream regulatory genes. To infer the functions of these genes, human uterine smooth muscle cell lines overexpressing SATB2 or NRG1 genes were established (SATB2 or NRG1 lines), and their transcriptomes and pathways were analyzed. RESULTS:SATB2 and NRG1 were confirmed to be hypermethylated and upregulated in most uterine leiomyoma specimens (nine to 11 of the 11 cases). Among the established cell lines, morphological changes from spindle-like forms to fibroblast-like forms with elongated protrusions were observed in only the SATB2 line. Pathway analysis revealed that WNT/?-catenin and TGF-? signaling pathways which are related to the pathogenesis of uterine leiomyomas were activated in both SATB2 and NRG1 lines. In addition, signaling of growth factors including VEGF, PDGF, and IGF1, and retinoic acid signaling were activated in the SATB2 and NRG1 lines, respectively. CONCLUSIONS:These results indicate that SATB2 and NRG1 overexpression induced many of the signaling pathways that are considered to be involved in the pathogenesis of uterine leiomyomas, suggesting that these genes have roles as upstream regulatory factors.

SUBMITTER: Sato S

PROVIDER: S-EPMC6885490 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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SATB2 and NGR1: potential upstream regulatory factors in uterine leiomyomas.

Sato Shun S Maekawa Ryo R Tamura Isao I Shirafuta Yuichiro Y Shinagawa Masahiro M Asada Hiromi H Taketani Toshiaki T Tamura Hiroshi H Sugino Norihiro N

Journal of assisted reproduction and genetics 20191114 11

<h4>Purpose</h4>We attempted to identify the genes involved in the pathogenesis of uterine leiomyomas, under a hypothesis that the aberrant expression of upstream regulatory genes caused by aberrant DNA methylation is involved in the onset and development of uterine leiomyomas.<h4>Methods</h4>To find such genes, we compared genome-wide mRNA expression and DNA methylation in uterine leiomyomas and adjacent normal myometrium. Analysis of the data by Ingenuity Pathway Analysis software identified S ...[more]

PMID: 31728810

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Project description:The present study aimed to screen potential biomarkers for uterine leiomyomas disease, particularly target genes associated with the mediator of RNA polymerase II transcription subunit 12 (MED12) mutation. The microarray data of GSE30673, including 10 MED12 wild-type myometrium, 8 MED12 mutation leiomyoma and 2 MED12 wild-type leiomyoma samples, were downloaded from the Gene Expression Omnibus database. Compared with myometrium samples, differently-expressed genes (DEGs) in the MED12 mutation and wild-type leiomyoma samples were identified using the Limma package. The two sets of DEGs obtained were intersected to screen common DEGs. The DEGs in the MED12 mutation and wild-type leiomyoma samples, and common DEGs were defined as group A, B and C. Gene Ontology (GO) and pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery online tool. Based on the Kyoto Encyclopedia of Genes and Genomes database, pathway relation networks were constructed. DEGs in GO terms and pathways were intersected to screen important DEGs. Subsequently, a gene co?expression network was constructed and visualized using Cytoscape software. Reverse transcription?quantitative polymerase chain reaction was used to detect the expression levels of important DEGs. A total of 1,258 DEGs in group A were screened, and enriched for extracellular matrix (ECM) organization and ECM?receptor interaction. In addition, a total of 1,571 DEGs in group B were enriched for cell adhesion. Furthermore, 391 DEGs were involved in extracellular matrix organization. Pathway relation networks of group A, B and C were constructed with nodes of 48, 39, and 28, respectively. Finally, 135 important DEGs were obtained, including Acyl?CoA synthetase medium?chain family member 3, protein S (?) (PROS1) and F11 receptor. A gene co?expression network with 68 nodes was constructed. The expression of caspase 1 (CASP1) and aldehyde dehydrogenase 1 family member A1 (ALDH1A1) was significant higher in SK?UT?1 compared with that in PHM1?31 cells, while the expression of PROS1 was significant lower in SK?UT?1 cells. These results that CASP1, ALDH1A1 and PROS1 may be potential biomarkers for uterine leiomyomas. Furthermore, hematopoietic prostaglandin D synthase and carbonyl reductase 3 (CBR3) may be particular genes associated with the MED12 mutation in this disease.

Dataset Information

SATB2 and NGR1: potential upstream regulatory factors in uterine leiomyomas.

Publications

SATB2 and NGR1: potential upstream regulatory factors in uterine leiomyomas.

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