Differential Expression of MED12-Associated Coding RNA Transcripts in Uterine Leiomyomas.

Differential Expression of MED12-Associated Coding RNA Transcripts in Uterine Leiomyomas.
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DOI:
10.3390/ijms24043742
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发表时间:
2023-02-13
影响因子:
5.6
通讯作者:
--
中科院分区:
生物学2区
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最近的研究表明,MED12外显子2的体细胞突变发生频率高达80%,并在平滑肌瘤的发病机制中发挥功能性作用。本研究的目的是阐明编码RNA转录本的表达谱在平滑肌瘤,有和没有这些突变,和他们配对的子宫肌层。下一代RNA测序(NGS)被用来系统地分析来自成对平滑肌瘤(n = 19)的差异表达的RNA转录本。差异分析表明,有394个基因仅在突变的肿瘤中差异表达和异常表达。这些基因主要参与细胞外成分的调节。在两个对照组中重叠的差异表达基因中,携带MED12突变的肿瘤中许多基因的基因表达变化幅度更大。虽然子宫肌层不表达MED12突变,但突变和非突变标本的子宫肌层转录组景观存在显著差异,其中调节对含氧化合物反应的基因改变最多。总之,MED12突变对肿瘤和子宫肌层中平滑肌瘤发病机制关键基因的表达具有深远的影响,这可能改变肿瘤的特征和生长潜力。
Recent studies have demonstrated that somatic MED12 mutations in exon 2 occur at a frequency of up to 80% and have a functional role in leiomyoma pathogenesis. The objective of this study was to elucidate the expression profile of coding RNA transcripts in leiomyomas, with and without these mutations, and their paired myometrium. Next-generation RNA sequencing (NGS) was used to systematically profile the differentially expressed RNA transcripts from paired leiomyomas (n = 19). The differential analysis indicated there are 394 genes differentially and aberrantly expressed only in the mutated tumors. These genes were predominantly involved in the regulation of extracellular constituents. Of the differentially expressed genes that overlapped in the two comparison groups, the magnitude of change in gene expression was greater for many genes in tumors bearing MED12 mutations. Although the myometrium did not express MED12 mutations, there were marked differences in the transcriptome landscape of the myometrium from mutated and non-mutated specimens, with genes regulating the response to oxygen-containing compounds being most altered. In conclusion, MED12 mutations have profound effects on the expression of genes pivotal to leiomyoma pathogenesis in the tumor and the myometrium which could alter tumor characteristics and growth potential.
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