Downregulation of hsa_circ_0026123 suppresses ovarian cancer cell metastasis and proliferation through the miR‑124‑3p/EZH2 signaling pathway.

Downregulation of hsa_circ_0026123 suppresses ovarian cancer cell metastasis and proliferation through the miR‑124‑3p/EZH2 signaling pathway.
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下调hsa_circ_0026123通过miR-124 - 3 p/EZH 2信号通路抑制卵巢癌细胞转移和增殖

DOI:
10.3892/ijmm.2020.4804
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发表时间:
2021-03
影响因子:
5.4
通讯作者:
Tong X
Tong X
中科院分区:
医学3区
文献类型:
--
作者:
Yang X;Wang J;Li H;Sun Y;Tong X

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环状RNAs(CircRNAs)在各种类型的癌症中发挥作用。本研究提示hSA_CIRC_0026123在卵巢癌中表达上调,这可能与其在卵巢癌中的作用有关。然而,hSA_CIRC_0026123在卵巢癌细胞侵袭和增殖中的作用尚不清楚。本研究利用卵泡组织和卵泡细胞系对hsa_circ_0026123的功能进行了研究。用荧光素酶报告基因检测hSA_CIRC_0026123、miR-124-3p与ZEST同源物增强子2(EZH_2)的相关性。RT-qPCR法和蛋白质印迹法分别进行基因和蛋白质表达分析。用裸鼠移植瘤检测肿瘤生长情况,有或没有hSA_CIRC_0026123下调。结果证实,hSA_CIRC_0026123在卵泡组织和细胞系中表达上调,而hSA_CIRC_0026123沉默抑制了细胞的增殖和迁移,在体内和体外实验中也抑制了肿瘤干细胞分化相关标志的表达。结果表明,hSA_CIRC_0026123下调通过miR-124-3p的“海绵”作用抑制了EZH_2的表达,救治实验和荧光素酶报告分析证实了这一点。结果表明,hSA_CIRC_0026123沉默通过miR-124-3p/EZH_2信号通路抑制卵巢癌细胞的生长。总体而言,研究结果表明,hSA_CIRC_0026123基因敲除通过调节miR-124-3p/EZH_2轴来抑制卵巢癌细胞的进展。该方法可用于OVA的靶向治疗,也可作为OVA诊断和治疗的候选生物标志物。
Circular RNAs (circRNAs) play a role in various types of cancer. The present study suggested that hsa_ circ_0026123 expression was upregulated in ovarian cancer (OVA), which was associated with its role in OVA. However, the role of hsa_circ_0026123 in OVA cell invasion and proliferation remains unclear. In the present study, OVA tissues and cell lines were used to investigate the functions of hsa_circ_0026123. The associations between hsa_circ_0026123, miR-124-3p and enhancer of zeste homolog 2 (EZH2) were examined using a luciferase reporter assay. RT-qPCR and western blot analysis were used for gene and protein expression analysis, respectively. Tumor growth was detected using nude mouse tumor xenografts derived from SKOV3 cells, with or without hsa_circ_0026123 downregulation. The results confirmed that hsa_circ_0026123 expression was upregulated in OVA tissues and cell lines, while hsa_circ_0026123 silencing suppressed cell proliferation and migration; it also suppressed the expression of cancer stem cell (CSC) differentiation-related markers in either in vivoor in vitro experiments. The data revealed that hsa_circ_0026123 downregulation suppressed EZH2 expression by miR-124-3p 'sponging', which was confirmed by rescue experiments and luciferase reporter assays. The results revealed that hsa_circ_0026123 silencing suppressed ovarian cancer cell progression via the miR-124-3p/EZH2 signaling pathway. Overall, the findings demonstrated that hsa_circ_0026123 knockdown inhibited OVA cell progression by regulating the miR-124-3p/EZH2 axis. This methodology may thus be used for the targeted therapy of OVA, as well as a candidate biomarker for the diagnosis and treatment of OVA.
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