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Circ-ABCB10 knockdown inhibits the malignant progression of cervical cancer through microRNA-128-3p/ZEB1 axis
Biological Procedures Online ( IF 6.4 ) Pub Date : 2021-09-07 , DOI: 10.1186/s12575-021-00154-8
Wei Feng 1 , Dongya Zhang 1 , Ruitao Zhang 1
Affiliation  

We focused on the detailed functions of circ-ABCB10 in cervical cancer (CC) development and its mechanisms. The increasing findings have proposed the central roles of circular RNAs (circRNAs) in the tumorigenesis of various human cancers. Circ-ABCB10 displays promising oncogenic effect in several tumors. Circ-ABCB10 and miR-128-3p production levels in CC tissues and cells were tested through RT-qPCR. The association of circ-ABCB10 expression with clinicopathologic parameters of CC patients was statistically analyzed. Cell proliferation, invasion, apoptosis, and epithelial-mesenchymal transition (EMT) were evaluated by MTT, transwell invasion assays, flow cytometry analyses, and western blot examination of EMT markers. The binding activity between miR-128-3p and circ-ABCB10 or zinc finger E-box binding homeobox 1 (ZEB1) was explored through pull-down assay or luciferase reporter assay. The influence of circ-ABCB10 on CC tumorigenesis was evaluated by in vivo xenograft experiments. The elevated circ-ABCB10 expression was determined in CC tissues and cells. Moreover, higher production level of circ-ABCB10 was close related to lymph-node metastasis, Federation of Gynecology and Obstetrics (FIGO) stage, and tumor size in CC patients. Loss of circ-ABCB10 weakened cell proliferative and invasive abilities, inhibited EMT, and induced apoptosis in CC. Loss of circ-ABCB10 inhibited ZEB1 expression by serving as a sponge of miR-128-3p in CC cells. Circ-ABCB10 sponged miR-128-3p to enhance cell proliferation, invasion, EMT and inhibit apoptosis in CC cells. Xenograft tumor assays confirmed that circ-ABCB10 knockdown inhibited CC tumor growth. Our study suggests that circ-ABCB10 depletion inhibits proliferation, invasion and EMT and promotes apoptosis of cervical cancer cells through miR-128-3p/ZEB1 axis and represses CC tumor growth.

中文翻译:

Circ-ABCB10敲低通过microRNA-128-3p/ZEB1轴抑制宫颈癌的恶性进展

我们重点研究了circ-ABCB10在宫颈癌(CC)发展中的详细功能及其机制。越来越多的发现提出了环状 RNA (circRNA) 在各种人类癌症的肿瘤发生中的核心作用。Circ-ABCB10 在多种肿瘤中显示出有希望的致癌作用。通过 RT-qPCR 测试 CC 组织和细胞中 Circ-ABCB10 和 miR-128-3p 的产生水平。统计分析circ-ABCB10表达与CC患者临床病理参数的关系。通过 MTT、Transwell 侵袭实验、流式细胞术分析和 EMT 标记物的蛋白质印迹检查来评估细胞增殖、侵袭、凋亡和上皮间质转化 (EMT)。通过 Pull-down 测定或荧光素酶报告基因测定探索 miR-128-3p 与 circ-ABCB10 或锌指 E-box 结合同源盒 1 (ZEB1) 之间的结合活性。通过体内异种移植实验评估了circ-ABCB10对CC肿瘤发生的影响。在 CC 组织和细胞中测定了 circ-ABCB10 表达升高。此外,circ-ABCB10的较高产生水平与CC患者的淋巴结转移、妇产科联合会(FIGO)分期和肿瘤大小密切相关。circ-ABCB10 的缺失会削弱细胞的增殖和侵袭能力,抑制 EMT,并诱导 CC 细胞凋亡。circ-ABCB10 的缺失通过充当 CC 细胞中 miR-128-3p 的海绵来抑制 ZEB1 表达。Circ-ABCB10 吸收 miR-128-3p 来增强 CC 细胞的增殖、侵袭、EMT 并抑制细胞凋亡。异种移植肿瘤测定证实 circ-ABCB10 敲低可抑制 CC 肿瘤生长。我们的研究表明,circ-ABCB10 缺失可抑制增殖、侵袭和 EMT,并通过 miR-128-3p/ZEB1 轴促进宫颈癌细胞凋亡,并抑制 CC 肿瘤生长。
更新日期:2021-09-07
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