环状RNA hsa_circ_0007121通过子痫前期中miR-182-5p/PGF轴调节滋养层细胞的增殖、迁移、侵袭和上皮-间质转化。
Circular RNA hsa_circ_0007121 regulates proliferation, migration, invasion, and epithelial-mesenchymal transition of trophoblast cells by miR-182-5p/PGF axis in preeclampsia.
作者信息
Gai Shukun, Sun Li, Wang Huiying, Yang Ping
机构信息
Department of Obstetrics, Yantai Yuhuangding Hospital, 20 Yudong Road, Zhifu District, Shandong Province, 264000, Yantai, Shandong, China.
出版信息
Open Med (Wars). 2020 Oct 14;15(1):1061-1071. doi: 10.1515/med-2020-0230. eCollection 2020.
BACKGROUND
Mounting evidence has revealed that abnormal expression of circular RNAs play pivotal roles in many human diseases including preeclampsia (PE). While human sapiens circular RNA 0007121 (hsa_circ_0007121) has been verified to be downregulated in human placental tissues, the underlying mechanisms were still unclear. This research aims to investigate the effect and underlying mechanisms of hsa_circ_0007121 in preeclampsia.
METHODS
The expression of hsa_circ_0007121, microRNA (miR)-182-5p, and placental growth factor (PGF) was assessed by quantitative reverse transcription polymerase chain reaction in PE placentas relative to the expression in normal pregnancy placentas. After transfection, cell counting kit-8 assay was employed to detect cell proliferation. Cell migration and invasion were tested by the transwell assay. The relative level of epithelial-mesenchymal transition (EMT)-related proteins in HTR-8/SVneo cells and PGF in placentas samples were measured by western blot. The relationship between miR-182-5p and hsa_circ_0007121 or PGF was predicated by circular RNA interactome or ENCORI and verified by dual-luciferase reporter assay and RNA immunoprecipitation assay.
RESULTS
The levels of hsa_circ_0007121 and PGF were significantly declined in PE placental tissues and HTR-8/SVneo cells, whereas miR-182-5p had an opposite result. Downregulation of hsa_circ_0007121 obviously inhibited HTR-8/SVneo cell proliferation, migration, invasion, and EMT, while upregulation of hsa_circ_0007121 promoted this process. Besides, miR-182-5p was a target gene of hsa_circ_0007121 and could target PGF. Further analysis indicated that hsa_circ_0007121 regulated the proliferation, migration, invasion, and EMT of HTR-8/SVneo cells via altering PGF expression by interacting with miR-182-5p.
CONCLUSION
Hsa_circ_0007121 mediated the progression of PE via miR-182-5p/PGF axis.
背景
越来越多的证据表明，环状RNA的异常表达在包括子痫前期（PE）在内的许多人类疾病中起关键作用。虽然已证实人类环状RNA 0007121（hsa_circ_0007121）在人胎盘组织中表达下调，但其潜在机制仍不清楚。本研究旨在探讨hsa_circ_0007121在子痫前期中的作用及潜在机制。
方法
通过定量逆转录聚合酶链反应评估子痫前期胎盘组织中hsa_circ_0007121、微小RNA（miR）-182-5p和胎盘生长因子（PGF）的表达，并与正常妊娠胎盘组织中的表达进行比较。转染后，采用细胞计数试剂盒-8法检测细胞增殖。通过Transwell实验检测细胞迁移和侵袭能力。采用蛋白质免疫印迹法检测HTR-8/SVneo细胞中上皮-间质转化（EMT）相关蛋白及胎盘组织中PGF的相对水平。通过环状RNA相互作用组或ENCORI预测miR-182-5p与hsa_circ_0007121或PGF之间的关系，并通过双荧光素酶报告基因实验和RNA免疫沉淀实验进行验证。
结果
子痫前期胎盘组织和HTR-8/SVneo细胞中hsa_circ_0007121和PGF水平显著下降，而miR-182-5p水平则相反。下调hsa_circ_0007121明显抑制HTR-8/SVneo细胞增殖、迁移、侵袭和EMT，而上调hsa_circ_0007121则促进这一过程。此外，miR-182-5p是hsa_circ_0007121的靶基因，且可靶向PGF。进一步分析表明，hsa_circ_0007121通过与miR-182-5p相互作用改变PGF表达，从而调节HTR-8/SVneo细胞的增殖、迁移、侵袭和EMT。
结论
Hsa_circ_0007121通过miR-182-5p/PGF轴介导子痫前期的进展。
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