Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, Republic of Korea.
College of Medicine, Konyang University, Daejeon 35365, Republic of Korea.
Genes (Basel). 2024 Feb 15;15(2):244. doi: 10.3390/genes15020244.
The primary goal of this investigation was to identify mRNA targets affected by dysregulated miRNAs in RIF. This was accomplished by comprehensively analyzing mRNA and miRNA expression profiles in two groups: female subjects with normal reproductive function (control, n = 5) and female subjects experiencing recurrent implantation failure (RIF, n = 5). We conducted transcriptome sequencing and small RNA sequencing on endometrial tissue samples from these cohorts. Subsequently, we validated a selection of intriguing findings using real-time PCR with samples from the same cohort. In total, our analysis revealed that 929 mRNAs exhibited differential expression patterns between the control and RIF patient groups. Notably, our investigation confirmed the significant involvement of dysregulated genes in the context of RIF. Furthermore, we uncovered promising correlation patterns within these mRNA/miRNA pairs. Functional categorization of these miRNA/mRNA pairs highlighted that the differentially expressed genes were predominantly associated with processes such as angiogenesis and cell adhesion. We identified new target genes that are regulated by miR-665, including Blood Vessel Epicardial Substance (BVES) and Adenosylhomocysteinase like 2 (AHCYL2). Our findings suggest that abnormal regulation of genes involved in angiogenesis and cell adhesion, including BVES and AHCYL2, contributes to the endometrial dysfunction observed in women with recurrent implantation failure (RIF) compared to healthy women.
本研究的主要目的是鉴定 RIF 中失调 miRNA 影响的 mRNA 靶标。通过对两组女性（对照组，n=5；复发性植入失败组，RIF，n=5）的 mRNA 和 miRNA 表达谱进行全面分析来实现。我们对来自这些队列的子宫内膜组织样本进行了转录组测序和小 RNA 测序。随后，我们使用相同队列的样本通过实时 PCR 验证了一些有趣的发现。总的来说，我们的分析显示，在对照组和 RIF 患者组之间，有 929 个 mRNAs 表现出差异表达模式。值得注意的是，我们的研究证实了失调基因在 RIF 背景下的显著参与。此外，我们在这些 mRNA/miRNA 对中发现了有前景的关联模式。对这些 miRNA/mRNA 对进行功能分类，突出显示差异表达基因主要与血管生成和细胞黏附等过程相关。我们鉴定了新的受 miR-665 调控的靶基因，包括血管内皮细胞外基质（BVES）和腺苷同型半胱氨酸酶样 2（AHCYL2）。我们的研究结果表明，与健康女性相比，复发性植入失败（RIF）女性中涉及血管生成和细胞黏附的基因异常调节，包括 BVES 和 AHCYL2，导致了子宫内膜功能障碍。
