de Almeida Bruna Cristine, Dos Anjos Laura Gonzalez, Kagohara Luciane Tsukamoto, Al-Hendy Ayman, Yang Qiwei, Baracat Edmund Chada, Coutinho-Camillo Cláudia Malheiros, Carvalho Katia Candido
Laboratório de Ginecologia Estrutural e Molecular (LIM 58), Disciplina de Ginecologia, Departamento de Obstetricia e Ginecologia, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Cerqueira Cesar, São Paulo 05403-010, Brazil.
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21231, USA.
Biomedicines. 2025 Feb 23;13(3):560. doi: 10.3390/biomedicines13030560.
We have previously identified , , , , and as differentially expressed between uterine leiomyoma (LM) and leiomyosarcoma (LMS) tissue samples. The present study aimed to characterize these miRNA expression profiles and to assess the functional role of and in uterine LM and LMS cells. All the selected miRNAs showed downregulation in LMS cells compared to LM cells, but only and expression patterns matched those of patient samples. Therefore, these two miRs were selected for further analyses. Loss of function analysis demonstrated that and silencing inhibited LM cell proliferation and migration. silencing induced and expression and inhibited , , and in LM. Silencing of promotes and expression in LM and diminishes , , , , and . Gain of function analysis revealed that the introduction of and mimics suppressed proliferation and migration in malignant LMS cells. Additionally, transfection with a mimic downregulated and expression and enhanced the expression of , , and in LMS cells. Moreover, overexpression decreased , , , and expression and increased the expression of in this cell. Importantly, the single introduction of either a or mimic was able to decrease the invasion capacity of LMS cells. Our studies demonstrated that or may play an anti-oncogenic role in uterine tumors; further studies are needed to better understand the role and regulatory mechanism of these miRNAs in LMS cancer development, which will help provide prognostic and therapeutic options for patients with LMS.
我们之前已鉴定出……（此处原文部分内容缺失，无法完整翻译）在子宫平滑肌瘤（LM）和子宫平滑肌肉瘤（LMS）组织样本之间存在差异表达。本研究旨在表征这些miRNA表达谱，并评估……（此处原文部分内容缺失，无法完整翻译）在子宫LM和LMS细胞中的功能作用。与LM细胞相比，所有选定的miRNA在LMS细胞中均表现出下调，但只有……（此处原文部分内容缺失，无法完整翻译）的表达模式与患者样本匹配。因此，选择这两种miR进行进一步分析。功能丧失分析表明，……（此处原文部分内容缺失，无法完整翻译）的沉默抑制了LM细胞的增殖和迁移。……（此处原文部分内容缺失，无法完整翻译）的沉默诱导了……（此处原文部分内容缺失，无法完整翻译）在LM中的表达，并抑制了……（此处原文部分内容缺失，无法完整翻译）。……（此处原文部分内容缺失，无法完整翻译）的沉默促进了……（此处原文部分内容缺失，无法完整翻译）在LM中的表达，并降低了……（此处原文部分内容缺失，无法完整翻译）。功能获得分析表明，引入……（此处原文部分内容缺失，无法完整翻译）模拟物可抑制恶性LMS细胞的增殖和迁移。此外，用……（此处原文部分内容缺失，无法完整翻译）模拟物转染可下调……（此处原文部分内容缺失，无法完整翻译）的表达，并增强LMS细胞中……（此处原文部分内容缺失，无法完整翻译）的表达。此外，……（此处原文部分内容缺失，无法完整翻译）的过表达降低了……（此处原文部分内容缺失，无法完整翻译）的表达，并增加了该细胞中……（此处原文部分内容缺失，无法完整翻译）的表达。重要的是，单独引入……（此处原文部分内容缺失，无法完整翻译）或……（此处原文部分内容缺失，无法完整翻译）模拟物均能够降低LMS细胞的侵袭能力。我们的研究表明，……（此处原文部分内容缺失，无法完整翻译）或……（此处原文部分内容缺失，无法完整翻译）可能在子宫肿瘤中发挥抑癌作用；需要进一步研究以更好地了解这些miRNA在LMS癌症发展中的作用和调控机制，这将有助于为LMS患者提供预后和治疗选择。
