Combined targeting of TCF7L1/2, PTEN, CDK6, and BCCIP by microRNA miR-29c-3p is associated with reduced invasion and proliferation of endometriotic cells.

IF 2.7 3区 医学 Q2 OBSTETRICS & GYNECOLOGY
Reproductive Medicine and Biology Pub Date : 2025-03-25 eCollection Date: 2025-01-01 DOI:10.1002/rmb2.12645
Teresa Helene Wentges, Heba M El-Shorafa, Janine Beckmann, Michael Gabriel, Matti Poutanen, Burkhard Greve, Ludwig Kiesel, Sebastian D Schäfer, Martin Götte
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引用次数: 0

Abstract

Purpose: Endometriosis is a chronic gynecological disorder associated with pain symptoms and infertility. The expression of microRNA miR-29c-3p is dysregulated in endometriosis. We aimed to identify novel molecular targets of miR-29c-3p functionally linked to proliferation and invasive growth in endometriosis.

Methods: The epithelial endometriotic cell line 12Z and primary endometriotic stromal cells (PESC) were transfected with control miRNA or pre-miR-29c-3p, and subjected to cell cycle analysis, cell viability, wound healing, and Matrigel invasion assays. Expression of bioinformatically predicted miR-29c-3p targets was analyzed by qPCR and western blot. Target gene expression in endometriotic lesions and healthy endometrium was studied in the EndometDB endometriosis database.

Results: miR-29c-3p decreased 12Z and PESC cell viability and the proportion of PESC in the S-phase. 12Z cell invasion, but not migration, was decreased after miR-29c-3p upregulation. miR-29c-3p decreased the mRNA expression of CDK6, BCCIP, TCF7L1, TCF7L2, PTEN, COL4A1, E-Cadherin, and N-Cadherin. A decrease of CDK6 and PTEN and an increase of p21 were confirmed at the protein level. EndometDB database analysis demonstrated dysregulated expression of the selected targets in both deep endometriosis and ovarian endometriosis.

Conclusions: miR-29c-3p effectively curbs endometriotic cell proliferation and invasion by combined inhibition of cell cycle regulators and transcription factors, unveiling a promising therapeutic strategy.

microRNA miR-29c-3p联合靶向TCF7L1/2、PTEN、CDK6和BCCIP与减少子宫内膜异位症细胞的侵袭和增殖有关。
目的:子宫内膜异位症是一种慢性妇科疾病,与疼痛症状和不孕有关。microRNA miR-29c-3p在子宫内膜异位症中表达失调。我们旨在确定miR-29c-3p在子宫内膜异位症中与增殖和侵袭性生长功能相关的新分子靶点。方法:用对照miRNA或pre-miR-29c-3p转染上皮性子宫内膜异位症细胞系12Z和原发性子宫内膜异位症基质细胞(PESC),进行细胞周期分析、细胞活力、创面愈合和Matrigel侵袭试验。通过qPCR和western blot分析生物信息学预测的miR-29c-3p靶点的表达。在子宫内膜异位症数据库EndometDB中研究了靶基因在子宫内膜异位症病变和健康子宫内膜中的表达。结果:miR-29c-3p降低12Z和PESC细胞活力及s期PESC比例。miR-29c-3p上调后,12Z细胞的侵袭性降低,但迁移性不降低。miR-29c-3p降低CDK6、BCCIP、TCF7L1、TCF7L2、PTEN、COL4A1、E-Cadherin、N-Cadherin mRNA的表达。在蛋白水平上证实CDK6和PTEN降低,p21升高。EndometDB数据库分析显示,在深部子宫内膜异位症和卵巢子宫内膜异位症中,所选靶点的表达都异常。结论:miR-29c-3p通过联合抑制细胞周期调节因子和转录因子,有效抑制子宫内膜异位症细胞的增殖和侵袭,揭示了一种有前景的治疗策略。
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来源期刊
CiteScore
5.70
自引率
5.90%
发文量
53
审稿时长
20 weeks
期刊介绍: Reproductive Medicine and Biology (RMB) is the official English journal of the Japan Society for Reproductive Medicine, the Japan Society of Fertilization and Implantation, the Japan Society of Andrology, and publishes original research articles that report new findings or concepts in all aspects of reproductive phenomena in all kinds of mammals. Papers in any of the following fields will be considered: andrology, endocrinology, oncology, immunology, genetics, function of gonads and genital tracts, erectile dysfunction, gametogenesis, function of accessory sex organs, fertilization, embryogenesis, embryo manipulation, pregnancy, implantation, ontogenesis, infectious disease, contraception, etc.
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