Circular RNAs feature prominently in cancer development. Nonetheless, the role of circ_0072088 in hepatocellular carcinoma (HCC) remains unclear. GEO databases (GSE97332, GSE108724, GSE36915, and GSE33006) were used to screen out the differentially expressed circRNAs, miRNAs, and mRNA in HCC. The expressions of circ_0072088, miR-375, and Janus Kinase 2 (JAK2) mRNA in HCC tissue and cell lines were determined with quantitative real-time polymerase chain reaction. RNase R treatment assay was used to measure the stability of circ_0072088, and subcellular fraction assay was used to detect the localization of circ_0072088. Cell counting kit-8 assay, flow cytometry, and Transwell assay were used to measure proliferation, apoptosis, migration, and invasion of HCC cells. RNA immunoprecipitation and dual-luciferase reporter gene assay were employed for investigating the binding sequence between circ_0072088 and miR-375, as well as miR-375 and JAK2 3′UTR. Western blot assay was used to detect the expression of JAK2 and p-STAT3 after circ_0072088 and miR-375 were selectively regulated. Circ_0072088 and JAK2 mRNA expressions were highly expressed in HCC tissues and cell lines while miR-375 expression was remarkably downregulated. Circ_0072088 was resistant to RNase R treatment and mainly located in the cytoplasm of HCC cells. The transfection of circ_0072088 overexpression plasmid or miR-375 inhibitors promoted the proliferation, migration, and invasion, and inhibited the apoptosis of HCC cells, whereas transfection of circ_0072088 siRNA or miR-375 mimics exerted opposite effects. Besides, miR-375 was confirmed as a target of circ_0072088 and miR-375 could further downregulate the expression of JAK2. MiR-375 mimics could reverse the upregulation of JAK2 and p-STAT3 protein induced by circ_0072088 overexpression. Circ_0072088 can enhance the proliferation, migration, and invasion, and impede apoptosis of HCC cells. Mechanistically, circ_0072088 activates JAK2/STAT3 signaling pathway by serving as a molecular sponge of miR-375.

中文翻译：

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Circ_0072088 通过 miR-375 激活 JAK2/STAT3 信号通路促进肝细胞癌的进展

环状 RNA 在癌症发展中具有显着的特征。尽管如此，circ_0072088 在肝细胞癌 (HCC) 中的作用仍不清楚。GEO数据库（GSE97332、GSE108724、GSE36915和GSE33006）用于筛选HCC中差异表达的circRNA、miRNA和mRNA。通过定量实时聚合酶链反应测定 HCC 组织和细胞系中 circ_0072088、miR-375 和 Janus Kinase 2 (JAK2) mRNA 的表达。用RNase R处理法检测circ_0072088的稳定性，用亚细胞组分检测法检测circ_0072088的定位。细胞计数 kit-8 测定、流式细胞术和 Transwell 测定用于测量 HCC 细胞的增殖、凋亡、迁移和侵袭。RNA免疫沉淀和双荧光素酶报告基因测定用于研究circ_0072088和miR-375以及miR-375和JAK2 3'UTR之间的结合序列。Western blot检测circ_0072088和miR-375选择性调控后JAK2和p-STAT3的表达。Circ_0072088 和 JAK2 mRNA 表达在 HCC 组织和细胞系中高表达，而 miR-375 表达显着下调。Circ_0072088 对 RNase R 处理具有抗性，主要位于 HCC 细胞的细胞质中。转染circ_0072088过表达质粒或miR-375抑制剂促进HCC细胞的增殖、迁移和侵袭，抑制细胞凋亡，而转染circ_0072088 siRNA或miR-375模拟物则发挥相反的作用。除了，miR-375 被证实是 circ_0072088 的靶点，miR-375 可以进一步下调 JAK2 的表达。MiR-375 模拟物可以逆转由 circ_0072088 过表达诱导的 JAK2 和 p-STAT3 蛋白的上调。Circ_0072088 可以增强 HCC 细胞的增殖、迁移和侵袭能力，并阻止细胞凋亡。从机制上讲，circ_0072088 通过充当 miR-375 的分子海绵激活 JAK2/STAT3 信号通路。