CircETV6 acts as an oncogenic driver in hepatocellular carcinoma progression

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2024-08-31 DOI:10.1002/jbt.23766
Xiaoqin Li, Xuemei Jiang, Jing Lu, Lan Jiang, Yan Li, Yuting Lin, Feng Wan, Changmin Wang
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Abstract

Circular RNA (circRNA) plays important role in hepatocellular carcinoma (HCC) progression. However, the role and mechanism of circETV6 in HCC progression remain unclear. The levels of circETV6, ETV6, miR-383-5p, and PTPRE were tested by quantitative reverse-transcription polymerase chain reaction. Cell functions were assessed using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, 5-ethynyl-2′-deoxyuridine assay, colony formation assay, wound healing assay, transwell assay, and flow cytometry. The protein levels of poptosis-related markers and PTPRE were determined by western blot analysis. RNA interaction was analyzed by dual-luciferase reporter assay and RNA pull-down assay. A xenograft model was established to assess circETV6 roles in vivo. CircETV6 was highly expressed in HCC tissues and cells. CircETV6 knockdown repressed HCC cell proliferation, migration, invasion, and cell cycle, while accelerated apoptosis. CircETV6 targeted miR-383-5p, and miR-383-5p inhibition reversed the regulation of circETV6 knockdown on HCC cell progression. CircETV6 promoted PTPRE level via targeting miR-383-5p. Overexpressed PTPRE abolished the inhibition effect of miR-383-5p on HCC cell progression. In addition, circETV6 knockdown slowed HCC tumor growth in vivo. CircETV6 might facilitate HCC progression via the miR-383-5p/PTPRE axis, providing a novel target for HCC treatment.

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CircETV6 是肝细胞癌发展过程中的致癌驱动因子
环状 RNA(circRNA)在肝细胞癌(HCC)进展过程中发挥着重要作用。然而,circETV6在HCC进展中的作用和机制仍不清楚。研究人员通过反转录聚合酶链式反应定量检测了 circETV6、ETV6、miR-383-5p 和 PTPRE 的水平。细胞功能的评估采用了 3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2H-溴化四氮唑试验、5-乙炔基-2′-脱氧尿苷试验、集落形成试验、伤口愈合试验、透孔试验和流式细胞术。通过 Western 印迹分析确定了凋亡相关标记物和 PTPRE 的蛋白水平。通过双荧光素酶报告实验和 RNA pull-down 实验分析了 RNA 相互作用。建立了异种移植模型来评估 circETV6 在体内的作用。CircETV6 在 HCC 组织和细胞中高表达。CircETV6的敲除抑制了HCC细胞的增殖、迁移、侵袭和细胞周期,同时加速了细胞凋亡。CircETV6靶向miR-383-5p,抑制miR-383-5p可逆转circETV6敲除对HCC细胞进展的调控。CircETV6通过靶向miR-383-5p促进PTPRE水平。过表达的 PTPRE 可消除 miR-383-5p 对 HCC 细胞进展的抑制作用。此外,circETV6基因敲除可减缓HCC肿瘤在体内的生长。CircETV6可能通过miR-383-5p/PTPRE轴促进HCC的进展,为HCC治疗提供了一个新的靶点。
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CiteScore
7.20
自引率
4.30%
发文量
567
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