Department of Obstetrics, Huai'an maternal and child health care center, Huai'an, China.
Am J Reprod Immunol. 2022 Nov;88(5):e13609. doi: 10.1111/aji.13609. Epub 2022 Aug 30.
One of the important reasons for the development of preeclampsia (PE) is the abnormal function of trophoblast cells. Many circular RNAs (circRNAs) have been confirmed to participate in the regulation of trophoblast cell function to mediate PE progression. However, whether circ_0077109 is involved in PE progression through regulating trophoblast cell function remains unclear.
Quantitative real-time PCR was utilized for measuring the expression of circ_0077109, microRNA (miR)-139-5p and homeobox D10 (HOXD10). Trophoblast cell proliferation, apoptosis, invasion, and angiogenesis was assessed cell counting kit 8 assay, EdU assay, flow cytometry, transwell assay and tube formation assay. In addition, western blot analysis was used to determine protein expression. The interaction between miR-139-5p and circ_0077109 or HOXD10 was verified by dual-luciferase reporter assay and RIP assay.
Our results pointed out that circ_0077109 was a circRNA with upregulated expression in PE patients. Overexpression of circ_0077109 suppressed trophoblast cell proliferation, invasion, and angiogenesis, while increased apoptosis. MiR-139-5p was found to be sponged by circ_0077109, and its mimic reversed the suppressive effect of circ_0077109 on trophoblast cell function. HOXD10 was a target of miR-139-5p, and its overexpression inhibited trophoblast cell proliferation, invasion, and angiogenesis. MiR-139-5p inhibitor could repress trophoblast cell function, while this effect could be reversed by HOXD10 knockdown.
In summary, we confirmed that circ_0077109 inhibited trophoblast cell function through the regulation of miR-139-5p/HOXD10 axis, which might be a potential target for PE treatment.
子痫前期（PE）发展的一个重要原因是滋养细胞功能异常。许多环状 RNA（circRNA）已被证实参与调节滋养细胞功能，从而介导 PE 的进展。然而，circ_0077109 是否通过调节滋养细胞功能参与 PE 的进展尚不清楚。
采用实时定量 PCR检测 circ_0077109、微小 RNA（miR）-139-5p 和同源盒 D10（HOXD10）的表达。通过细胞计数试剂盒 8 检测、EdU 检测、流式细胞术、Transwell 检测和管形成检测评估滋养细胞增殖、凋亡、侵袭和血管生成。此外，采用 Western blot 分析检测蛋白表达。通过双荧光素酶报告基因检测和 RIP 检测验证 miR-139-5p 与 circ_0077109 或 HOXD10 的相互作用。
我们的结果表明，circ_0077109 是 PE 患者中上调表达的 circRNA。circ_0077109 的过表达抑制滋养细胞增殖、侵袭和血管生成，同时增加凋亡。发现 miR-139-5p 被 circ_0077109 海绵吸附，其模拟物逆转了 circ_0077109 对滋养细胞功能的抑制作用。HOXD10 是 miR-139-5p 的靶基因，过表达抑制滋养细胞增殖、侵袭和血管生成。miR-139-5p 抑制剂可抑制滋养细胞功能，而 HOXD10 敲低可逆转该作用。
总之，我们证实 circ_0077109 通过调节 miR-139-5p/HOXD10 轴抑制滋养细胞功能，这可能是治疗 PE 的潜在靶点。
