Chuang Tsai-Der, Rysling Shawn, Ton Nhu, Baghdasarian Daniel, Khorram Omid
The Lundquist Institute for Biomedical Innovation, Torrance, CA 90502, USA.
Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Torrance, CA 90509, USA.
Int J Mol Sci. 2025 Jul 16;26(14):6798. doi: 10.3390/ijms26146798.
Uterine fibroids (leiomyomas) are benign tumors whose growth is influenced by estrogen and progesterone. This study aimed to compare the profiles of differentially expressed long non-coding RNAs (lncRNAs) in fibroids from postmenopausal and premenopausal women to identify hormone-responsive lncRNAs. RNA sequencing was performed on six pairs of fibroid (Fib) and adjacent myometrium (Myo) tissues from postmenopausal women. Out of 7876 normalized lncRNAs, 3684 were differentially expressed (≥1.5-fold), with 1702 upregulated and 1982 downregulated in Fib. Comparative analysis with a previously published premenopausal dataset identified 741 lncRNAs that were altered based on their menopausal status, including 62 lncRNAs that were uniquely dysregulated in postmenopausal samples. Overall, 9 lncRNAs were selected for validation by PCR in an expanded cohort of 31 postmenopausal and 84 premenopausal paired samples. Several lncRNAs, including , , , , and , were upregulated in premenopausal Fib but not in postmenopausal ones, while displayed the opposite pattern. and were elevated in Fib from both groups, although the increase was less pronounced in the postmenopausal group. was significantly downregulated in postmenopausal Fib, with no change observed in premenopausal samples. Additionally, analysis based on MED12 mutation status revealed that lncRNAs such as , , and showed limited or reduced differential expression (mutation-positive vs. mutation-negative) in postmenopausal patients compared to the premenopausal group. These findings indicate that lncRNA expression in fibroids is modulated by menopausal status, likely reflecting hormonal influence. Hormone-responsive lncRNAs may play key roles in fibroid pathogenesis and represent potential targets for therapeutic intervention.
子宫肌瘤（平滑肌瘤）是一种良性肿瘤，其生长受雌激素和孕激素影响。本研究旨在比较绝经后和绝经前女性子宫肌瘤中差异表达的长链非编码RNA（lncRNA）谱，以鉴定激素反应性lncRNA。对6对绝经后女性的子宫肌瘤（Fib）和相邻子宫肌层（Myo）组织进行了RNA测序。在7876个标准化lncRNA中，3684个差异表达（≥1.5倍），其中1702个在Fib中上调，1982个下调。与先前发表的绝经前数据集进行比较分析，鉴定出741个基于绝经状态而改变的lncRNA，包括62个在绝经后样本中独特失调的lncRNA。总体而言，在31对绝经后和84对绝经前配对样本的扩大队列中，选择了9个lncRNA通过PCR进行验证。包括 、 、 、 和 在内的几种lncRNA在绝经前Fib中上调，但在绝经后Fib中未上调，而 表现出相反的模式。两组Fib中的 和 均升高，尽管在绝经后组中升高不太明显。 在绝经后Fib中显著下调，在绝经前样本中未观察到变化。此外，基于MED12突变状态的分析表明，与绝经前组相比，绝经后患者中 、 和 等lncRNA的差异表达有限或降低（突变阳性与突变阴性）。这些发现表明，子宫肌瘤中lncRNA的表达受绝经状态调节，可能反映了激素的影响。激素反应性lncRNA可能在子宫肌瘤发病机制中起关键作用，并代表治疗干预的潜在靶点。
