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Journal of Assisted Reproduction and Genetics

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01-11-2019 | Reproductive Physiology and Disease

SATB2 and NGR1: potential upstream regulatory factors in uterine leiomyomas

Authors: Shun Sato, Ryo Maekawa, Isao Tamura, Yuichiro Shirafuta, Masahiro Shinagawa, Hiromi Asada, Toshiaki Taketani, Hiroshi Tamura, Norihiro Sugino

Published in: Journal of Assisted Reproduction and Genetics | Issue 11/2019

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/β-catenin and TGF-β 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.

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Title: SATB2 and NGR1: potential upstream regulatory factors in uterine leiomyomas
Authors: Shun Sato
Ryo Maekawa
Isao Tamura
Yuichiro Shirafuta
Masahiro Shinagawa
Hiromi Asada
Toshiaki Taketani
Hiroshi Tamura
Norihiro Sugino
Publication date: 01-11-2019
Publisher: Springer US
Published in: Journal of Assisted Reproduction and Genetics / Issue 11/2019
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI: https://doi.org/10.1007/s10815-019-01582-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

SATB2 and NGR1: potential upstream regulatory factors in uterine leiomyomas

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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