CircRNA UBAP2 serves as a sponge of miR-1294 to increase tumorigenesis in hepatocellular carcinoma through regulating c-Myc expression
CircRNA UBAP2 serves as a sponge of miR-1294 to increase tumorigenesis in hepatocellular carcinoma through regulating c-Myc expression
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CircRNA UBAP2 作为 miR-1294 的海绵，通过调节 c-Myc 表达来增加肝细胞癌的肿瘤发生
DOI：
10.1093/carcin/bgab068
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发表时间：
2021-07-27
期刊：
影响因子：
4.7
通讯作者：
Huang, Cheng
中科院分区：
文献类型：
--
作者：
Yu, Min-Cheng;Ding, Guang-Yu;Huang, Cheng
环状RNA（circRNA）是一类在健康和疾病组织中具有复杂作用的调控RNA。然而，circRNA在肝细胞癌（HCC）中的致癌作用仍然知之甚少，包括环状泛素结合相关蛋白2（circUBAP 2）促进肿瘤发生的机制。我们通过实时定量聚合酶链反应分析了20对HCC和健康组织样本以及7个HCC细胞系中circUBAP 2的表达。进行功能实验，如CCK 8活力测定、集落形成测定、伤口愈合、transwell测定和流式细胞术，以评估circUBAP 2的体外作用。为了进一步阐明circUBAP 2的作用机制，我们进行了双荧光素酶测定、蛋白质印迹、RNA下拉测定和拯救实验。CircUBAP 2在大多数HCC组织中高度上调，并且与不良预后相关。circUBAP 2高表达的HCC患者血管浸润更严重，分化更差。在功能上，circUBAP 2过表达增强HCC细胞增殖、迁移和侵袭，并抑制凋亡。此外，我们发现circUBAP 2通过海绵状miR-1294上调c-Myc表达，从而促进肝癌发生。在HCC中抑制circUBAP 2表达减弱了c-Myc的致癌作用。这些发现表明circUBAP 2促进HCC生长和转移。CircUBAP 2可能作为一种独立的预后生物标志物或作为治疗HCC的新靶点具有价值。
Circular RNAs (circRNAs) are a class of regulatory RNAs with complex roles in healthy and diseased tissues. However, the oncogenic role of circRNAs in hepatocellular carcinoma (HCC) remains poorly understood, including the mechanisms by which the circular ubiquitin-binding associated protein 2 (circUBAP2) contributes to tumorigenesis. We analyzed the expression of circUBAP2 in 20 paired samples of HCC and healthy tissue as well as in seven HCC cell lines via quantitative real-time polymerase chain reaction. Functional experiments, such as CCK8 viability assays, colony formation assays, wound healing, transwell assays and flow cytometry, were conducted to assess the effects of circUBAP2 in vitro. To further elucidate the mechanisms by which circUBAP2 acts, we conducted dual-luciferase assays, western blots, RNA pull-down assays and rescue experiments. CircUBAP2 was highly upregulated in most HCC tissues and was associated with poor prognosis. HCC patients with high circUBAP2 expression had greater vascular invasion and worse differentiation. Functionally, circUBAP2 overexpression enhanced HCC cell proliferation, migration and invasion and inhibited apoptosis. Furthermore, we found that circUBAP2 upregulated c-Myc expression by sponging miR-1294, thus contributing to hepatocarcinogenesis. Inhibiting circUBAP2 expression in HCC attenuated the oncogenic effects of c-Myc. These findings suggest that circUBAP2 promotes HCC growth and metastasis. CircUBAP2 may have value as an independent prognostic biomarker or as a new target for the treatment of HCC.