Hepatocellular carcinoma (HCC) ranks third in the cause of death due to cancer. Circular RNA circSEC24 Homolog A (circSEC24A) has been uncovered to be upregulated in liver cancer. However, the function of circSEC24A in HCC is indistinct. We analyzed the microarray datasets GSE78520 and GSE94508 to search for differentially expressed circRNAs associated with HCC. Expression of circSEC24A, microRNA (miR)-455-3p, and protein phosphatase, Mg2+/Mn2+ dependent 1F (PPM1F) mRNA was detected by quantitative real-time polymerase chain reaction (RT-qPCR). Loss-of-function experiments were conducted to validate the biological function of circSEC24A in HCC cells in vitro and in vivo. Protein levels were evaluated by western blotting and immunohistochemistry (IHC). The relationship between circSEC24A or PPM1F and miR-455-3p was verified by a dual-luciferase reporter and/or RNA immunoprecipitation (RIP) assays. circSEC24A was overexpressed in HCC. circSEC24A silencing decreased xenograft tumor growth in vivo and repressed proliferation, metastasis, invasion, epithelial-to-mesenchymal transition (EMT), induced cell cycle arrest, and apoptosis of HCC cells in vitro. circSEC24A acted as a molecular sponge to sequester miR-455-3p, resulting in elevating the expression of PPM1F. miR-455-3p inhibitor reversed the suppressive impact of circSEC24A silencing on malignant behaviors of HCC cells. PPM1F overexpression offsets the inhibitory effect of miR-455-3p mimic on malignant behaviors of HCC cells. circSEC24A sponged miR-455-3p to elevate the PPM1F expression, resulting in accelerating malignant behaviors of HCC cells. The study provided a potential therapeutic target for patients with HCC.

中文翻译：

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CircSEC24A 通过在肝细胞癌中隔离 miR-455-3p 促进肿瘤进展。

肝细胞癌 (HCC) 在癌症导致的死亡原因中排名第三。环状 RNA circSEC24 同源物 A (circSEC24A) 已被发现在肝癌中被上调。然而，circSEC24A在HCC中的功能尚不清楚。我们分析了微阵列数据集 GSE78520 和 GSE94508，以寻找与 HCC 相关的差异表达的 circRNA。通过定量实时聚合酶链反应 (RT-qPCR) 检测 circSEC24A、microRNA (miR)-455-3p 和蛋白磷酸酶、Mg2+/Mn2+ 依赖性 1F (PPM1F) mRNA 的表达。进行功能丧失实验以验证 circSEC24A 在体外和体内 HCC 细胞中的生物学功能。通过蛋白质印迹和免疫组织化学 (IHC) 评估蛋白质水平。circSEC24A 或 PPM1F 与 miR-455-3p 之间的关系通过双荧光素酶报告基因和/或 RNA 免疫沉淀 (RIP) 分析进行了验证。circSEC24A 在 HCC 中过度表达。circSEC24A 沉默降低了体内异种移植肿瘤的生长，并抑制了体外 HCC 细胞的增殖、转移、侵袭、上皮间质转化 (EMT)、诱导细胞周期停滞和凋亡。circSEC24A 充当分子海绵来隔离 miR-455-3p，从而提高 PPM1F 的表达。miR-455-3p 抑制剂逆转了 circSEC24A 沉默对 HCC 细胞恶性行为的抑制作用。PPM1F 过表达抵消了 miR-455-3p 模拟物对 HCC 细胞恶性行为的抑制作用。circSEC24A 吸附 miR-455-3p 以提高 PPM1F 表达，导致加速 HCC 细胞的恶性行为。该研究为 HCC 患者提供了一个潜在的治疗靶点。