The First Affiliated Hospital, Department of Gastroenterology and Hepatology, Hengyang Medical School, University of South China, Hengyang, China.
Department of Gastroenterology, Zibo Central Hospital of Shandong Province, Zibo, China.
J Gastroenterol Hepatol. 2021 Dec;36(12):3457-3468. doi: 10.1111/jgh.15635. Epub 2021 Aug 23.
Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide. Recent researches have shown that circular RNAs (circRNAs) could affect the progress of HCC, but the mechanism is still indistinct. In this work, we explored the roles of circRNA_0016788 in HCC.
The levels of hsa_circ_0016788, microRNA-506-3p (miR-506-3p), and mRNA of poly-adenosine diphosphate-ribose polymerase, member 14 (PARP14) were detected by quantitative real-time reverse transcription-polymerase chain reaction in HCC tissues. Meanwhile, the level of PARP14 was quantified by Western blot analysis. Besides, the cell functions were examined by commercial kit, Cell Counting Kit-8 assay, EdU assay, colony formation assay, flow cytometry assay, Western blot, and transwell assay. Furthermore, the interplay between miR-506-3p and hsa_circ_0016788 or PARP14 was detected by dual-luciferase reporter assay. Eventually, the in vivo experiments were applied to measure the role of hsa_circ_0016788.
The levels of hsa_circ_0016788 and PARP14 were upregulated, and the miR-506-3p level was decreased in HCC tissues in contrast to that in normal tissues. For functional analysis, hsa_circ_0016788 deficiency inhibited cell glycolysis metabolism, cell vitality, cell proliferation, colony formation, and invasion in HCC cells whereas promoted cell apoptosis. Moreover, miR-506-3p was confirmed to repress the progression of HCC cells by suppressing PARP14. In mechanism, hsa_circ_0016788 acted as a miR-506-3p sponge to regulate the level of PARP14. In addition, hsa_circ_0016788 knockdown also inhibited tumor growth in vivo.
Hsa_circ_0016788 facilitates the development of HCC through increasing PARP14 expression by regulating miR-506-3p, which also offered an underlying targeted therapy for HCC treatment.
肝细胞癌（HCC）是一种常见的恶性肿瘤，全球范围内均有发生。最近的研究表明，环状 RNA（circRNA）可能影响 HCC 的进展，但机制尚不清楚。在本研究中，我们探讨了 circRNA_0016788 在 HCC 中的作用。
采用实时定量逆转录聚合酶链反应检测 HCC 组织中 hsa_circ_0016788、微小 RNA-506-3p（miR-506-3p）和多聚腺苷二磷酸核糖聚合酶 14（PARP14）mRNA 的水平。同时，采用 Western blot 分析检测 PARP14 水平。此外，通过商业试剂盒、细胞计数试剂盒-8 检测、EdU 检测、集落形成检测、流式细胞术检测、Western blot 和 Transwell 检测来检测细胞功能。进一步通过双荧光素酶报告基因检测来检测 miR-506-3p 与 hsa_circ_0016788 或 PARP14 之间的相互作用。最后，通过体内实验来测量 hsa_circ_0016788 的作用。
与正常组织相比，HCC 组织中 hsa_circ_0016788 和 PARP14 水平上调，miR-506-3p 水平下调。功能分析显示，hsa_circ_0016788 缺失抑制 HCC 细胞的糖酵解代谢、细胞活力、细胞增殖、集落形成和侵袭，而促进细胞凋亡。此外，miR-506-3p 通过抑制 PARP14 来抑制 HCC 细胞的进展。在机制上，hsa_circ_0016788 作为 miR-506-3p 的海绵来调节 PARP14 的水平。此外，hsa_circ_0016788 敲低也抑制了体内肿瘤的生长。
hsa_circ_0016788 通过调节 miR-506-3p 增加 PARP14 的表达促进 HCC 的发展，为 HCC 的治疗提供了潜在的靶向治疗靶点。
