circRNA_000926 regulates proliferation and apoptosis of cervical cancer cells by targeting miR-411-5p / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨环状RNA _000926（circ_000926）对宫颈癌细胞增殖和凋亡的影响及其作用机制。方法: 收集2019年5月至2020年9月河北医科大学第一医院手术切除的30例宫颈癌患者的癌及癌旁组织标本，以及人宫颈癌细胞HeLa、SiHa和正常宫颈细胞Ect1/E6E7，用qPCR法检测组织和细胞中circ_000926和miR-411-5p的表达水平。将circ_000926过表达质粒及空白质粒、circ_000926小干扰RNA及阴性对照寡核苷酸、miR-411-5p mimic和阴性对照质粒分别转染HeLa和SiHa细胞，分为pc-circ_000926组、pc-NC组、si-circ_000926组、si-NC组、miR-411-5p mimic组和miR-NC组。通过CCK-8法检测转染细胞的增殖活力，TUNEL法检测细胞的凋亡水平。通过双荧光素酶报告基因实验验证circ_000926与miR-411-5p之间的靶向关系，WB法检测细胞中Ki67、BAX、Caspase-3和Caspase-9蛋白的表达。结果: 与癌旁组织和Ect1/E6E7细胞相比，宫颈癌组织和HeLa、SiHa细胞中circ_000926表达显著升高、miR-411-5p表达显著降低（均P<0.01）。与pc-NC组相比，pc-circ_000926组细胞增殖活力显著增强、细胞凋亡率显著降低（均P<0.01），细胞中miR-411-5p表达显著降低、Ki67蛋白表达显著升高，BAX、Caspase-3、Caspase-9蛋白表达显著降低（均P<0.01）。与si-NC组相比，si-circ_000926组细胞增殖活力显著降低、细胞凋亡率显著升高（均P<0.01），细胞中miR-411-5p表达显著升高、Ki67蛋白表达显著降低，BAX、Caspase-3和Caspase-9蛋白表达显著升高（均P<0.01）。双荧光素酶报告基因实验结果证实circ_000926靶向负向调控miR-411-5p表达，过表达miR-411-5p可逆转过表达circ_000926对宫颈癌细胞增殖和凋亡的作用。结论: circ_000926通过靶向吸附miR-411-5p促进宫颈癌细胞的增殖，并抑制细胞凋亡。

Differential expression of microRNA-411 and 376c is associated with hypertension in pregnancy

Preeclampsia is a major reason of morbidity and mortality in pregnant women and perinatal fetus. Hence, it is of prime importance that diagnostic markers are defined to predict chances of preeclampsia in pregnant women. It has been previously shown that microRNA (miRNA)-376c expression is decreased in the placenta of preeclampsia patients at term. Even though this decrease was not mimicked in the placenta at the pre-term stage, miR-376c expression was decreased in the plasma of these patients as early as the second trimester. Plasma and placenta specimens were obtained from pregnant women having unifetal gestation undergoing perinatal care between January 2014 and December 2016 (n=49). Early trimester placentas were collected from patients undergoing terminated pregnancies through dilation and curettage procedure. Our results showed that in addition to miR-376c, miR-441 levels were decreased in the placenta of preeclampsia patients, and this decrease occurred both at pre-term and at term. This decrease is also mimicked in the plasma levels at both early and late weeks of pregnancy, highlighting that miR-441 levels can serve as a diagnostic marker of risk of preeclampsia in pregnant women. Overexpression of the miR-441, as well as miR-376c, promoted cell viability, migration, and invasion in the human immortalized cytotrophoblast cell line HTR8/SVneo, indicating that their decrease in pregnant women would result in anomalous apoptosis and functional imbalance resulting in premature abortion and other complications. MiR-441 level can thus potentially serve as diagnostic marker of preeclampsia in pregnant women.