The Influence of Race/Ethnicity on the Transcriptomic Landscape of Uterine Fibroids

Abstract

The objective of this study was to determine if the aberrant expression of select genes could form the basis for the racial disparity in fibroid characteristics. The next-generation RNA sequencing results were analyzed as fold change [leiomyomas/paired myometrium, also known as differential expression (DF)], comparing specimens from White (n = 7) and Black (n = 12) patients. The analysis indicated that 95 genes were minimally changed in tumors from White (DF ≈ 1) but were significantly altered by more than 1.5-fold (up or down) in Black patients. Twenty-one novel genes were selected for confirmation in 69 paired fibroids by qRT-PCR. Among these 21, coding of transcripts for the differential expression of FRAT2, SOX4, TNFRSF19, ACP7, GRIP1, IRS4, PLEKHG4B, PGR, COL24A1, KRT17, MMP17, SLN, CCDC177, FUT2, MYO5B, MYOG, ZNF703, CDC25A, and CDCA7 was significantly higher, while the expression of DAB2 and CAV2 was significantly lower in tumors from Black or Hispanic patients compared with tumors from White patients. Western blot analysis revealed a greater differential expression of PGR-A and total progesterone (PGR-A and PGR-B) in tumors from Black compared with tumors from White patients. Collectively, we identified a set of genes uniquely expressed in a race/ethnicity-dependent manner, which could form the underlying mechanisms for the racial disparity in fibroids and their associated symptoms.

Targeting the long non-coding RNA MIAT for the treatment of fibroids in an animal model

“…Informed consent was obtained from all the participants. Portions of the tumors were used for in vivo studies and the remainder, along with myometrium, was snap-frozen in liquid nitrogen for molecular analysis [ 16 , 17 ].…”

The Effect of Race/Ethnicity and MED12 Mutation on the Expression of Long Non-Coding RNAs in Uterine Leiomyoma and Myometrium

“…One microgram of total RNA from each tissue was used to produce strand-specific cDNA libraries using the Truseq (Illumina, San Diego, CA, USA) according to manufacturer's instructions. The RNA sequencing was carried out at Novogene Corporation Inc., (Sacramento, CA, USA) and bioinformatics analysis was performed as previously described [19,20]. To visualize the strength of differential gene expression, the Hierarchical clustering and TreeView graph, volcano plot, principal component analysis (PCA) plot, and the Gene Ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) Pathway Enrichment Analysis plot were made using Flaski and NcPath [97,98], and the interactive network of lncRNA-miRNA-mRNA was analyzed and made with the ENCORI/starBase (Encyclopedia of RNA Interactomes) and Cytoscape software Version 3.10.1 [37,38,99].…”

“…Somatic MED12 mutation in exon 2 occurs at a frequency of 60 to 80% in leiomyomas and has a functional role in their initiation and progression, potentially through its influence on many important pathways, including the Wnt/β-catenin signaling, hedgehog signaling, sex steroid receptor signaling, and transforming growth factor (TGF)-β receptor signaling pathways [12][13][14]17,18]. We have previously reported on the differential expression of protein-coding genes, some of which are influenced by race and MED12 mutation of the tumor [19,20].…”