Hon Jing-Xian, Wahab Norhazlina Abdul, Karim Abdul Kadir Abdul, Mokhtar Norfilza Mohd, Mokhtar Mohd Helmy
Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia.
GUT Research Group, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia.
Biomedicines. 2024 Sep 28;12(10):2218. doi: 10.3390/biomedicines12102218.
: Patients with endometriosis still respond poorly to progestins due to progesterone resistance associated with microRNAs (miRNAs). The aim of this study was to investigate the expression of selected miRNAs, estrogen receptor (ER)α, ERβ, progesterone receptor (PR)-A and PR-B and to determine the target genes of upregulated miRNAs in endometriosis. : In this study, 18 controls, 18 eutopic and 18 ectopic samples were analysed. Profiling and validation of miRNAs associated with functions of endometriosis were performed using next-generation sequencing (NGS) and qRT-PCR. At the same time, the expression of ERα, ERβ, PR-A and PR-B was also determined using qRT-PCR. Target prediction was also performed for miR-199a-3p, miR-1-3p and miR-125b-5p using StarBase. : In this study, NGS identified seven significantly differentially expressed miRNAs, of which six miRNAs related to the role of endometriosis were selected for validation by qRT-PCR. The expression of miR-199a-3p, miR-1-3p, miR-146a-5p and miR-125b-5p was upregulated in the ectopic group compared to the eutopic group. Meanwhile, ERα and ERβ were significantly differentially expressed in endometriosis compared to the control group. However, the expressions of PR-A and PR-B showed no significant differences between the groups. The predicted target genes for miR-199a-3p, miR-1-3p and miR-125b-5p are SCD, TAOK1, DDIT4, LASP1, CDK6, TAGLN2, G6PD and ELOVL6. : Our findings demonstrated that the expressions of ERα and ERβ might be regulated by miRNAs contributing to progesterone resistance, whereas the binding of miRNAs to target genes could also contribute to the pathogenesis of endometriosis. Therefore, miRNAs could be used as potential biomarkers and for targeted therapy in patients with endometriosis.
由于与微小RNA（miRNA）相关的孕酮抵抗，子宫内膜异位症患者对孕激素的反应仍然较差。本研究的目的是调查选定的miRNA、雌激素受体（ER）α、ERβ、孕激素受体（PR）-A和PR-B的表达，并确定子宫内膜异位症中上调的miRNA的靶基因。
在本研究中，分析了18例对照、18例在位内膜和18例异位内膜样本。使用下一代测序（NGS）和qRT-PCR对与子宫内膜异位症功能相关的miRNA进行分析和验证。同时，也使用qRT-PCR测定ERα、ERβ、PR-A和PR-B的表达。还使用StarBase对miR-199a-3p、miR-1-3p和miR-125b-5p进行靶标预测。
在本研究中，NGS鉴定出7种显著差异表达的miRNA，其中选择6种与子宫内膜异位症作用相关的miRNA通过qRT-PCR进行验证。与在位内膜组相比，异位内膜组中miR-199a-3p、miR-1-3p、miR-146a-5p和miR-125b-5p的表达上调。同时，与对照组相比，子宫内膜异位症中ERα和ERβ有显著差异表达。然而，PR-A和PR-B的表达在各组之间无显著差异。miR-199a-3p、miR-1-3p和miR-125b-5p的预测靶基因是SCD、TAOK1、DDIT4、LASP1、CDK6、TAGLN2、G6PD和ELOVL6。
我们的研究结果表明，ERα和ERβ的表达可能受导致孕酮抵抗的miRNA调控，而miRNA与靶基因的结合也可能促成子宫内膜异位症的发病机制。因此，miRNA可作为子宫内膜异位症患者潜在的生物标志物和靶向治疗手段。
