Lidocaine can inhibit the malignant development of various human cancers. Circular RNA (circRNA) dynein 1 heavy chain gene (circ_DYNC1H1) acted as a pro-cancer molecule in hepatocellular carcinoma (HCC). This study aimed to explore whether the function of lidocaine was related to the oncogenic circ_DYNC1H1 in HCC. Colony formation assay and 3-(4,5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay were used for proliferation detection. Cell apoptosis was assessed by flow cytometry, and migration or invasion was determined by the transwell assay. The levels of circ_DYNC1H1, microRNA-520a-3p (miR-520a-3p), and ubiquitin-specific protease 14 (USP14) were examined using the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Protein levels were measured using western blot. The binding between miR-520a-3p and circ_DYNC1H1 or USP14 was confirmed by the dual-luciferase reporter assay. In vivo assay was conducted by a xenograft model in mice. Lidocaine reduced proliferation, migration, and invasion but promoted apoptosis in HCC cells. The circ_DYNC1H1 expression was downregulated in lidocaine-treated HCC cells. The inhibitory effect of lidocaine on HCC progression was weakened after circ_DYNC1H1 overexpression. miR-520a-3p was a target of circ_DYNC1H1, and the function of lidocaine was related to the regulation of circ_DYNC1H1/miR-520a-3p axis. USP14 served as a target for miR-520a-3p, and circ_DYNC1H1 could sponge miR-520a-3p to regulate the USP14 expression. The lidocaine-induced suppression of HCC development was also achieved by mediating the miR-520a-3p/USP14 axis. In vivo assay revealed that lidocaine suppressed the tumor growth of HCC by reducing the expression of circ_DYNC1H1 to affect the levels of miR-520a-3p and USP14. Our results clarified that lidocaine impeded tumor progression via targeting the circ_DYNC1H1/miR-520a-3p/USP14 axis in HCC cells.

中文翻译：

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利多卡因通过 circ_DYNC1H1/miR-520a-3p/USP14 轴对肝细胞癌具有抗肿瘤作用

利多卡因可以抑制多种人类癌症的恶性发展。环状 RNA (circRNA) 动力蛋白 1 重链基因 (circ_DYNC1H1) 在肝细胞癌 (HCC) 中充当促癌分子。本研究旨在探讨利多卡因的功能是否与HCC中的致癌circ_DYNC1H1有关。菌落形成测定和 3-(4,5-二甲基噻唑-2-y1)-2, 5-二苯基溴化四唑 (MTT) 测定用于增殖检测。通过流式细胞术评估细胞凋亡，并通过transwell测定确定迁移或侵袭。使用定量逆转录酶聚合酶链反应 (qRT-PCR) 检测 circ_DYNC1H1、microRNA-520a-3p (miR-520a-3p) 和泛素特异性蛋白酶 14 (USP14) 的水平。使用蛋白质印迹测量蛋白质水平。体内通过小鼠异种移植模型进行测定。利多卡因减少了 HCC 细胞的增殖、迁移和侵袭，但促进了细胞凋亡。circ_DYNC1H1 表达在利多卡因处理的 HCC 细胞中下调。circ_DYNC1H1过表达后利多卡因对HCC进展的抑制作用减弱。miR-520a-3p是circ_DYNC1H1的靶点，利多卡因的作用与circ_DYNC1H1/miR-520a-3p轴的调节有关。USP14 作为 miR-520a-3p 的靶标，circ_DYNC1H1 可以海绵 miR-520a-3p 来调节 USP14 的表达。利多卡因诱导的 HCC 发展抑制也是通过介导 miR-520a-3p/USP14 轴实现的。体内分析表明，利多卡因通过降低 circ_DYNC1H1 的表达以影响 miR-520a-3p 和 USP14 的水平来抑制 HCC 的肿瘤生长。我们的研究结果阐明，利多卡因通过靶向 HCC 细胞中的 circ_DYNC1H1/miR-520a-3p/USP14 轴阻碍了肿瘤进展。