hsa_circ_0005243 的下调通过 β-连环蛋白和 NF-κB 途径诱导滋养细胞功能障碍和炎症。
Downregulation of hsa_circ_0005243 induces trophoblast cell dysfunction and inflammation via the β-catenin and NF-κB pathways.
机构信息
Department of Obstetrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, Jiangsu, China.
Department of Obstetrics, Changzhou Maternity and Child Health Care Hospital affiliated Hospital Affiliated to Nanjing Medical University, Changzhou, 213003, Jiangsu, China.
出版信息
Reprod Biol Endocrinol. 2020 May 20;18(1):51. doi: 10.1186/s12958-020-00612-0.
BACKGROUND
Gestational diabetes mellitus (GDM) is a common complication in pregnancy that poses a serious threat to the health of both mother and child. While the specific etiology and pathogenesis of this disease are not fully understood, it is thought to arise due to a combination of insulin resistance, inflammation, and genetic factors. Circular RNAs (circRNAs) are a special kind of non-coding RNA that have attracted significant attention in recent years due to their diverse activities, including a potential regulatory role in pregnancy-related diseases, such as GDM.
METHODS
We previously reported the existence of a novel circRNA, hsa_circ_0005243, which was identified by RNA sequencing. In this study, we examined its expression in 20 pregnant women with GDM and 20 normal pregnant controls using quantitative reverse transcription PCR analysis. Subsequent in vitro experiments were conducted following hsa_circ_0005243 knockdown in HTR-8/SVneo cells to examine the role of hsa_circ_0005243 in cell proliferation and migration, as well as the secretion of inflammatory factors such as tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). Finally, we examined the expression of β-catenin and nuclear factor kappa-B (NF-κB) signaling pathways to assess their role in GDM pathogenesis.
RESULTS
Expression of hsa_circ_0005243 was significantly reduced in both the placenta and plasma of GDM patients. Knockdown of hsa_circ_0005243 in trophoblast cells significantly suppressed cell proliferation and migration ability. In addition, increased secretion of inflammatory factors (TNF-α and IL-6) was observed after hsa_circ_0005243 depletion. Further analyses showed that knockdown of hsa_circ_0005243 reduced the expression of β-catenin and increased nuclear NF-κB p65 nuclear translocation.
CONCLUSIONS
Downregulation of hsa_circ_0005243 may be associated with the pathogenesis of GDM via the regulation of β-catenin and NF-κB signal pathways, suggesting a new potential therapeutic target for GDM.
背景
妊娠糖尿病（GDM）是一种常见的妊娠并发症，对母婴健康构成严重威胁。虽然这种疾病的确切病因和发病机制尚未完全了解，但据认为是由于胰岛素抵抗、炎症和遗传因素的综合作用引起的。环状 RNA（circRNA）是一种特殊的非编码 RNA，近年来因其多种活性而受到广泛关注，包括在妊娠相关疾病（如 GDM）中可能具有调节作用。
方法
我们之前通过 RNA 测序报告了一种新型 circRNA，hsa_circ_0005243 的存在。在这项研究中，我们使用定量逆转录 PCR 分析检查了 20 名 GDM 孕妇和 20 名正常妊娠对照者中其表达情况。随后，在 HTR-8/SVneo 细胞中进行 hsa_circ_0005243 敲低的体外实验，以检查 hsa_circ_0005243 在细胞增殖和迁移以及肿瘤坏死因子-α（TNF-α）和白细胞介素 6（IL-6）等炎症因子分泌中的作用。最后，我们检查了 β-连环蛋白和核因子 kappa-B（NF-κB）信号通路的表达，以评估其在 GDM 发病机制中的作用。
结果
GDM 患者的胎盘和血浆中 hsa_circ_0005243 的表达均显著降低。在滋养细胞中敲低 hsa_circ_0005243 可显著抑制细胞增殖和迁移能力。此外，在 hsa_circ_0005243 耗尽后观察到炎症因子（TNF-α和 IL-6）的分泌增加。进一步分析表明，hsa_circ_0005243 的敲低降低了 β-连环蛋白的表达并增加了核 NF-κB p65 的核易位。
结论
hsa_circ_0005243 的下调可能通过调节β-连环蛋白和 NF-κB 信号通路与 GDM 的发病机制有关，提示 GDM 的新的潜在治疗靶点。
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