Different DNA methylome, transcriptome and histological features in uterine fibroids with and without MED12 mutations
Abstract Somatic mutations in Mediator complex subunit 12 (MED12m) have been reported as a biomarker of uterine fibroids (UFs). However, the role of MED12m is still unclear in the pathogenesis of UFs. Therefore, we investigated the differences in DNA methylome, transcriptome, and histological featur...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-05-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-12899-7 |
| _version_ | 1817989721842778112 |
|---|---|
| author | Ryo Maekawa Shun Sato Tetsuro Tamehisa Takahiro Sakai Takuya Kajimura Kotaro Sueoka Norihiro Sugino |
| author_facet | Ryo Maekawa Shun Sato Tetsuro Tamehisa Takahiro Sakai Takuya Kajimura Kotaro Sueoka Norihiro Sugino |
| author_sort | Ryo Maekawa |
| collection | DOAJ |
| description | Abstract Somatic mutations in Mediator complex subunit 12 (MED12m) have been reported as a biomarker of uterine fibroids (UFs). However, the role of MED12m is still unclear in the pathogenesis of UFs. Therefore, we investigated the differences in DNA methylome, transcriptome, and histological features between MED12m-positive and -negative UFs. DNA methylomes and transcriptomes were obtained from MED12m-positive and -negative UFs and myometrium, and hierarchically clustered. Differentially expressed genes in comparison with the myometrium and co-expressed genes detected by weighted gene co-expression network analysis were subjected to gene ontology enrichment analyses. The amounts of collagen fibers and the number of blood vessels and smooth muscle cells were histologically evaluated. Hierarchical clustering based on DNA methylation clearly separated the myometrium, MED12m-positive, and MED12m-negative UFs. MED12m-positive UFs had the increased activities of extracellular matrix formation, whereas MED12m-negative UFs had the increased angiogenic activities and smooth muscle cell proliferation. The MED12m-positive and -negative UFs had different DNA methylation, gene expression, and histological features. The MED12m-positive UFs form the tumor with a rich extracellular matrix and poor blood vessels and smooth muscle cells compared to the MED12m-negative UFs, suggesting MED12 mutations affect the tissue composition of UFs. |
| first_indexed | 2024-04-14T00:50:20Z |
| format | Article |
| id | doaj.art-fffab38ce5a64d7188e8406443dfe912 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-14T00:50:20Z |
| publishDate | 2022-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-fffab38ce5a64d7188e8406443dfe9122022-12-22T02:21:49ZengNature PortfolioScientific Reports2045-23222022-05-0112111810.1038/s41598-022-12899-7Different DNA methylome, transcriptome and histological features in uterine fibroids with and without MED12 mutationsRyo Maekawa0Shun Sato1Tetsuro Tamehisa2Takahiro Sakai3Takuya Kajimura4Kotaro Sueoka5Norihiro Sugino6Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Yamaguchi University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Yamaguchi University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Yamaguchi University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Yamaguchi University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Yamaguchi University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Yamaguchi University Graduate School of MedicineAbstract Somatic mutations in Mediator complex subunit 12 (MED12m) have been reported as a biomarker of uterine fibroids (UFs). However, the role of MED12m is still unclear in the pathogenesis of UFs. Therefore, we investigated the differences in DNA methylome, transcriptome, and histological features between MED12m-positive and -negative UFs. DNA methylomes and transcriptomes were obtained from MED12m-positive and -negative UFs and myometrium, and hierarchically clustered. Differentially expressed genes in comparison with the myometrium and co-expressed genes detected by weighted gene co-expression network analysis were subjected to gene ontology enrichment analyses. The amounts of collagen fibers and the number of blood vessels and smooth muscle cells were histologically evaluated. Hierarchical clustering based on DNA methylation clearly separated the myometrium, MED12m-positive, and MED12m-negative UFs. MED12m-positive UFs had the increased activities of extracellular matrix formation, whereas MED12m-negative UFs had the increased angiogenic activities and smooth muscle cell proliferation. The MED12m-positive and -negative UFs had different DNA methylation, gene expression, and histological features. The MED12m-positive UFs form the tumor with a rich extracellular matrix and poor blood vessels and smooth muscle cells compared to the MED12m-negative UFs, suggesting MED12 mutations affect the tissue composition of UFs.https://doi.org/10.1038/s41598-022-12899-7 |
| spellingShingle | Ryo Maekawa Shun Sato Tetsuro Tamehisa Takahiro Sakai Takuya Kajimura Kotaro Sueoka Norihiro Sugino Different DNA methylome, transcriptome and histological features in uterine fibroids with and without MED12 mutations Scientific Reports |
| title | Different DNA methylome, transcriptome and histological features in uterine fibroids with and without MED12 mutations |
| title_full | Different DNA methylome, transcriptome and histological features in uterine fibroids with and without MED12 mutations |
| title_fullStr | Different DNA methylome, transcriptome and histological features in uterine fibroids with and without MED12 mutations |
| title_full_unstemmed | Different DNA methylome, transcriptome and histological features in uterine fibroids with and without MED12 mutations |
| title_short | Different DNA methylome, transcriptome and histological features in uterine fibroids with and without MED12 mutations |
| title_sort | different dna methylome transcriptome and histological features in uterine fibroids with and without med12 mutations |
| url | https://doi.org/10.1038/s41598-022-12899-7 |
| work_keys_str_mv | AT ryomaekawa differentdnamethylometranscriptomeandhistologicalfeaturesinuterinefibroidswithandwithoutmed12mutations AT shunsato differentdnamethylometranscriptomeandhistologicalfeaturesinuterinefibroidswithandwithoutmed12mutations AT tetsurotamehisa differentdnamethylometranscriptomeandhistologicalfeaturesinuterinefibroidswithandwithoutmed12mutations AT takahirosakai differentdnamethylometranscriptomeandhistologicalfeaturesinuterinefibroidswithandwithoutmed12mutations AT takuyakajimura differentdnamethylometranscriptomeandhistologicalfeaturesinuterinefibroidswithandwithoutmed12mutations AT kotarosueoka differentdnamethylometranscriptomeandhistologicalfeaturesinuterinefibroidswithandwithoutmed12mutations AT norihirosugino differentdnamethylometranscriptomeandhistologicalfeaturesinuterinefibroidswithandwithoutmed12mutations |