Circular RNA (circRNA) plays a key role in the development and progression of several diseases; however, its role in intrauterine adhesions (IUAs) is not well understood. This study aims to investigate the expression profiles and potential role of circRNA in IUA. RNA-sequencing was performed to screen for abnormally expressed circRNAs in TGF-β1-induced IUA endometrial stromal cell (ESC) model (IUA group) and an SMAD3 inhibitor, SIS3-treated IUA ESC model (SIS3 group). Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to uncover the key functions and pathways. Interaction networks were constructed and analyzed based on the competing endogenous RNA hypothesis of circRNA. CircRNAs were validated by Sanger sequencing and quantitative polymerase chain reaction (qPCR). Cell proliferation and apoptosis were measured using MTS and flow cytometry, respectively. The protein and mRNA expression levels of fibrosis-related proteins were measured using western blotting and reverse transcription–qPCR, respectively. A total of 66 circRNAs were differentially expressed between the IUA and SIS3 groups. CircPlekha7 was identified as one of the significantly upregulated circRNAs in the SIS3 group. Overexpression of circPlekha7 enhanced apoptosis, decreased the viability of ESCs, and suppressed the expression of α-SMA, collagen I, and SMAD3 in ESCs; whereas knockdown of circPlekha7 exhibited opposite results. Altogether, the results indicate that circPlekha7 plays an anti-fibrotic role in IUA and may serve as a promising prognostic biomarker for patients with IUA. Therefore, overexpression of circPlekha7 could be a potential treatment strategy for IUA.

中文翻译：

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CircPlekha7 通过调节子宫内膜基质细胞增殖和凋亡在宫腔粘连中发挥抗纤维化作用


环状RNA（circRNA）在多种疾病的发生和进展中发挥着关键作用；然而，其在宫腔粘连 (IUAs) 中的作用尚不清楚。本研究旨在研究 circRNA 在 IUA 中的表达谱和潜在作用。通过RNA测序筛选TGF-β1诱导的IUA子宫内膜基质细胞（ESC）模型（IUA组）和SMAD3抑制剂SIS3处理的IUA ESC模型（SIS3组）中异常表达的circRNA。进行基因本体富集和京都基因和基因组百科全书通路分析以揭示关键功能和通路。基于circRNA竞争性内源RNA假说构建并分析了相互作用网络。 CircRNA 通过桑格测序和定量聚合酶链反应 (qPCR) 进行验证。分别使用MTS和流式细胞术测量细胞增殖和凋亡。分别使用蛋白质印迹和逆转录 qPCR 测量纤维化相关蛋白的蛋白和 mRNA 表达水平。 IUA 组和 SIS3 组之间共有 66 个 circRNA 存在差异表达。 CircPlekha7 被确定为 SIS3 组中显着上调的 circRNA 之一。 circPlekha7 的过表达会增强细胞凋亡，降低 ESC 的活力，并抑制 ESC 中 α-SMA、胶原蛋白 I 和 SMAD3 的表达；而 circPlekha7 的敲低则表现出相反的结果。总而言之，结果表明 circPlekha7 在 IUA 中发挥抗纤维化作用，并可能作为 IUA 患者有希望的预后生物标志物。因此，circPlekha7 的过度表达可能是 IUA 的潜在治疗策略。