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miR-130b-5p 水平升高或 ELK1 沉默抑制宫颈癌干细胞的自我更新能力、增殖、迁移和侵袭能力,并促进其凋亡。

Elevated microRNA-130b-5p or silenced ELK1 inhibits self-renewal ability, proliferation, migration, and invasion abilities, and promotes apoptosis of cervical cancer stem cells.

机构信息

Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, China.

出版信息

IUBMB Life. 2021 Jan;73(1):118-129. doi: 10.1002/iub.2409. Epub 2020 Dec 8.

Abstract

Cervical cancer (CC) is the most familiar gynecological malignancy. With the poor prognosis of CC patients, this study explored the effect of microRNA (miR)-130b-5p targeting ELK1 expression on self-renewal ability and stemness of CC stem cells. The tissues of patients with CC or cervical benign lesions were collected. MiR-130b-5p and ELK1 expression was detected by reverse transcription quantitative polymerase chain reaction and western blot analysis. Human CC cell line Hela was cultured and the induced CC stem cells were introduced with miR-130b-5p mimic or silenced ELK1 to figure their roles in self-renewal ability, stemness, colony formation, proliferation, migration, invasion abilities, and apoptosis of CC stem cells. Tumor growth was detected in nude mice in vivo. The targeting relationship between miR-130b-5p and ELK1 was analyzed using bioinformatic prediction and dual luciferase reporter gene assay. Decreased miR-130b-5p and elevated ELK1 existed in CC tissues of patients. Up-regulated miR-130b-5p decreased ELK1 expression in CC stem cells. Elevated miR-130b-5p or silenced ELK1 inhibited self-renewal ability and stemness, colony formation, proliferation, migration and invasion abilities, promoted apoptosis of CC stem cells, as well as decreased the weight and volume of tumor in nude mice. ELK1 was found to be targeted by miR-130b-5p. Overexpression ELK1 effectively reversed the cellular phenotypic changes and tumor formation in vivo caused by up-regulation of miR-130b-5p. We conclude that up-regulated miR-130b-5p or silenced ELK1 inhibits CC stem cell growth.

摘要

宫颈癌(CC)是最常见的妇科恶性肿瘤。由于 CC 患者的预后较差,本研究探讨了 microRNA(miR)-130b-5p 靶向 ELK1 表达对 CC 干细胞自我更新能力和干性的影响。收集 CC 患者或宫颈良性病变患者的组织。通过逆转录定量聚合酶链反应和 Western blot 分析检测 miR-130b-5p 和 ELK1 的表达。培养人 CC 细胞系 Hela,并将诱导的 CC 干细胞引入 miR-130b-5p 模拟物或沉默的 ELK1,以研究它们在 CC 干细胞自我更新能力、干性、集落形成、增殖、迁移、侵袭能力和凋亡中的作用。体内在裸鼠中检测肿瘤生长。利用生物信息学预测和双荧光素酶报告基因检测分析 miR-130b-5p 与 ELK1 的靶向关系。患者 CC 组织中存在 miR-130b-5p 下调和 ELK1 上调。上调的 miR-130b-5p 降低了 CC 干细胞中的 ELK1 表达。上调 miR-130b-5p 或沉默 ELK1 抑制 CC 干细胞的自我更新能力和干性、集落形成、增殖、迁移和侵袭能力,促进 CC 干细胞凋亡,并减少裸鼠肿瘤的重量和体积。发现 ELK1 是 miR-130b-5p 的靶标。过表达 ELK1 有效逆转了 miR-130b-5p 上调引起的细胞表型变化和体内肿瘤形成。我们得出结论,上调 miR-130b-5p 或沉默 ELK1 抑制 CC 干细胞生长。

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