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环状 RNA circ_0091579 通过 miR-490-5p/CASC3 轴促进肝癌细胞增殖、迁移、侵袭和糖酵解。

Circular RNA circ_0091579 Promotes Hepatocellular Carcinoma Proliferation, Migration, Invasion, and Glycolysis Through miR-490-5p/CASC3 Axis.

机构信息

Department of Laboratory, Luhe Hospital Affiliated to Capital Medical University, Beijing, China.

Department of Research and Development Center, DAAN Gene Co., Ltd. of Sun Yat-Sen University, Guangzhou, China.

出版信息

Cancer Biother Radiopharm. 2021 Dec;36(10):863-878. doi: 10.1089/cbr.2019.3472. Epub 2020 Jul 14.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignancies with high invasion and metastasis capacities. Circular RNAs (circRNAs) were evidenced to take part in the progression of multifarious cancers, including HCC. However, the role of circ_0091579 in HCC progression has not been fully described. This study aimed to explore the function of circ_0091579 and its potential regulatory mechanism in the progression of HCC. The expression of circ_0091579, microRNA-490-5p (miR-490-5p), and cancer susceptibility candidate 3 (CASC3) in HCC tissues and cells was detected by quantitative real-time polymerase chain reaction. The circular characteristic and stability of circ_0091579 were verified by RNase R digestion and actinomycin D reaction assays. Cell proliferation, migration, and invasion were determined by methyl thiazolyl tetrazolium assay and Transwell assay, respectively. The level of glycolysis was evaluated by glucose consumption and lactate production. The levels of proteins were examined by Western blot. The interaction between miR-490-5p and circ_0091579 or CASC3 was certified by Dual-luciferase reporter assay. circ_0091579 and CASC3 were upregulated, while miR-490-5p was downregulated in HCC tissues and cells. Silencing of either circ_0091579 or CASC3 suppressed cell proliferation, migration, invasion, and glycolysis in HCC cells. Moreover, miR-490-5p was verified to directly bind to circ_0091579 and CASC3. Circ_0091579 upregulated CASC3 by sponging miR-490-5p in HCC cells to promote cell proliferation, invasion, and migration. circ_0091579 promoted cell proliferation, migration, invasion, and glycolysis partially through miR-490-5p/CASC3 axis in HCC cells.

摘要

肝细胞癌 (HCC) 是最常见的恶性肿瘤之一,具有较高的侵袭和转移能力。环状 RNA (circRNA) 被证明参与了多种癌症的进展,包括 HCC。然而,circ_0091579 在 HCC 进展中的作用尚未完全描述。本研究旨在探讨 circ_0091579 在 HCC 进展中的功能及其潜在的调节机制。通过实时定量聚合酶链反应检测 HCC 组织和细胞中 circ_0091579、微小 RNA-490-5p (miR-490-5p) 和癌症易感性候选基因 3 (CASC3) 的表达。通过 RNase R 消化和放线菌素 D 反应试验验证 circ_0091579 的环状特征和稳定性。通过噻唑蓝比色法和 Transwell 试验分别测定细胞增殖、迁移和侵袭。通过葡萄糖消耗和乳酸生成评估糖酵解水平。通过 Western blot 检测蛋白水平。通过双荧光素酶报告基因试验证实 miR-490-5p 与 circ_0091579 或 CASC3 的相互作用。circ_0091579 和 CASC3 在 HCC 组织和细胞中上调,而 miR-490-5p 下调。沉默 circ_0091579 或 CASC3 均可抑制 HCC 细胞的增殖、迁移、侵袭和糖酵解。此外,miR-490-5p 被证实可直接与 circ_0091579 和 CASC3 结合。circ_0091579 通过海绵吸附 miR-490-5p 在 HCC 细胞中上调 CASC3,促进细胞增殖、侵袭和迁移。circ_0091579 通过 miR-490-5p/CASC3 轴在 HCC 细胞中部分促进细胞增殖、迁移、侵袭和糖酵解。

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