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miRNA-214 通过调控 NLRP3 的表达促进宫颈癌细胞发生细胞焦亡并抑制其增殖。

MiRNA-214 promotes the pyroptosis and inhibits the proliferation of cervical cancer cells via regulating the expression of NLRP3.

机构信息

Department of gynecology, Yidu central hospital of Weifang, Qingzhou, Shandong262500, China.

Department of obstetrics, Affiliated hospital of Weifang medical university, Weifang, Shandong261031, China.

出版信息

Cell Mol Biol (Noisy-le-grand). 2020 Sep 30;66(6):59-64.

Abstract

Inflammasome mediates the maturation of interleukin-1β (IL-1β) and IL-18, triggers the pyroptosis and associates with multiple autoimmune diseases. In light of this, we hope to investigate the regulatory role of miRNA-214 in the inflammasome of cervical cancer. With the samples collected from 50 cervical cancer patients and 50 age-matched healthy subjects, real-time PCR and Western blotting were employed to detect the mRNA and/or protein expression profiles of the NOD-like receptor protein family, including NLRP1, NLRP3, NLRC4, Caspase-1, IL-1β, IL-18 and miR-214. Corresponding plasmids were used to transfect the Hela, HCC94, Siha or HUCEL normal cell lines to upregulate or downregulate the expression of targeted genes and to construct the cervical cancer models on rats. In addition, RT-PCR and Western blot were also considered to detect the expression of miR-214 and pyroptosis-related genes, while the pyroptosis of cells was evaluated by using the caspase-1 activity detection kit. Downregulation of miR-214 was found in the cervical cancer patients and the cervical cancer cell lines (** P <0.01), while overexpression of miR-214 could induce the pyroptosis of cervical cancer cell by targeting NLRP3. In cervical cancer patients, miR-214 and NLRP3 are downregulated, while upregulation of miR-214, by enhancing the expression of NLRP3, can advance the pyroptosis of cervical cancer cells. In addition, we, for the first time, clarify the correlation of cervical cancer with the miR-214 and NLRP3.

摘要

炎症小体介导白细胞介素-1β(IL-1β)和 IL-18 的成熟,触发细胞焦亡,并与多种自身免疫性疾病有关。有鉴于此,我们希望研究 miRNA-214 在宫颈癌炎症小体中的调节作用。我们收集了 50 例宫颈癌患者和 50 例年龄匹配的健康受试者的样本,通过实时 PCR 和 Western blot 检测 NOD 样受体蛋白家族(包括 NLRP1、NLRP3、NLRC4、Caspase-1、IL-1β、IL-18 和 miR-214)的 mRNA 和/或蛋白表达谱。相应的质粒被用于转染 Hela、HCC94、Siha 或 HUCEL 正常细胞系,上调或下调靶基因的表达,并在大鼠上构建宫颈癌模型。此外,我们还采用 RT-PCR 和 Western blot 检测 miR-214 和细胞焦亡相关基因的表达,同时使用 caspase-1 活性检测试剂盒评估细胞焦亡情况。我们发现宫颈癌患者和宫颈癌细胞系中 miR-214 表达下调(**P <0.01),而过表达 miR-214 可以通过靶向 NLRP3 诱导宫颈癌细胞焦亡。在宫颈癌患者中,miR-214 和 NLRP3 表达下调,而通过上调 miR-214 增强 NLRP3 的表达,可以促进宫颈癌细胞的焦亡。此外,我们首次阐明了宫颈癌与 miR-214 和 NLRP3 的相关性。

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