The circular RNA PVT1/miR-203/HOXD3 pathway promotes the progression of human hepatocellular carcinoma
The circular RNA PVT1/miR-203/HOXD3 pathway promotes the progression of human hepatocellular carcinoma
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环状RNA PVT1/miR-203/HOXD3通路促进人肝细胞癌的进展
DOI：
10.1242/bio.043687
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发表时间：
2019-09-01
期刊：
影响因子：
2.4
通讯作者：
Wang, Fang
中科院分区：
文献类型：
--
作者：
Zhu, Yiqing;Liu, Yan;Wang, Fang
摘要 越来越多的证据表明环状RNA（circRNA）在各种生理和病理过程中发挥着重要作用。在本研究中，我们探讨了 circRNA PVT1 在肝细胞癌 (HCC) 中的作用。 qRT-PCR检测HCC组织和细胞系中circPVT1的相对表达量。通过细胞计数试剂盒 8 (CCK-8) 测定、乙炔基脱氧尿苷 (EdU) 掺入测定、transwell 测定、流式细胞术和体内异种移植物生长来评估 circPVT1 在 HCC 中的致癌作用。此外，还进行了生物信息学、荧光素酶报告基因检测和挽救实验，以确定 circPVT1 在 HCC 中的潜在机制。 HCC组织中检测到circPVT1表达增强，这与HCC患者的不良预后密切相关。 circPVT1 的敲低降低了体外 HCC 细胞系的增殖和迁移能力。相反，circPVT1 的上调改善了 HCC 细胞的生长和迁移。从机制上讲，我们发现 circPVT1 可以直接与 miR-203 结合，并通过调节 miR-203/homebox D3 (HOXD3) 通路促进 HCC 的发生和进展。总之，我们的研究表明，circPVT1 通过 miR-203/同源盒 D3 (HOXD3) 途径参与 HCC 的进展，并可能代表 HCC 治疗的潜在治疗靶点。摘要：我们的研究首次描述了 circPVT1 在 HCC 发生和进展中的作用。 CircPVT1可作为HCC早期筛查的潜在生物标志物。
ABSTRACT Accumulating evidence suggests that circular RNAs (circRNAs) play important roles in various physiological and pathological processes. In the present study, we explored the role of circRNA PVT1 in hepatocellular carcinoma (HCC). qRT-PCR was performed to detect the relative expression of circPVT1 in HCC tissues and cell lines. The oncogenic roles of circPVT1 in HCC were evaluated by cell counting kit-8 (CCK-8) assay, ethynyl deoxyuridine (EdU) incorporation assays, transwell assays, flow cytometry and in vivo xenograft growth. Furthermore, bioinformatics, luciferase reporter assays and rescue experiments were conducted to determine the underlying mechanism of circPVT1 in HCC. Enhanced circPVT1 expression was detected in HCC tissues, which was closely associated with poor prognosis of patients with HCC. Knockdown of circPVT1 decreased the proliferation and migration ability of HCC cell lines in vitro. Conversely, upregulation of circPVT1 improved the growth and migration in HCC cells. Mechanistically, we found that circPVT1 could bind directly to miR-203 and contributed to the initiation and progression of HCC by regulating miR-203/homebox D3 (HOXD3) pathway. In conclusion, our study reveals that circPVT1 participates in the progression of HCC through the miR-203/homeobox D3 (HOXD3) pathway and might represent a potential therapeutic target for HCC treatment. Summary: Our research is the first to characterize the role of circPVT1 in the initiation and progression of HCC. CircPVT1 could be applied as a potential biomarker for the early screening of HCC.