Data_Sheet_1_Upregulated hsa_circ_0005785 Facilitates Cell Growth and Metastasis of Hepatocellular Carcinoma Through the miR-578/APRIL Axis.docx

Although accumulating documents have expounded the pivotal position of circular RNAs (circRNAs) in hepatocarcinogenesis and progression, the overwhelming majority of their functions and molecular mechanisms in hepatocellular carcinoma (HCC) are elusive. Herein, we explored the functions and potential mechanisms of hsa_circ_0005785 in HCC, which was aberrantly overexpressed in HCC and related to HCC patients' TNM stage and overall survival. Moreover, hsa_circ_0005785 depletion could repress proliferation and metastasis of the HCC cell in vitro, lead to cell apoptosis and cell-cycle arrest, and restrain HCC cell growth in vivo. Furthermore, mechanism analyses discovered that hsa_circ_0005785 adsorbed miR-578 by playing a miRNA sponge role, which resulted in the derepression of a proliferation-inducing ligand (APRIL) expression, miR-578's mRNA target. Besides, hsa_circ_0005785 reversed the suppressive influence of miR-578 on HCC and accelerated tumor malignant progression through the miR-578/APRIL axis. Taken together, our current study revealed an oncogenic role of hsa_circ_0005785 in the tumorigenesis of HCC. Moreover, targeting to the hsa_circ_0005785/miR-578/APRIL regulatory pathway might be a promising diagnostic and therapeutic strategy for HCC clinical practice.

尽管众多累积文献已阐述环状RNA（circRNAs）在肝细胞癌发生和发展中的关键地位，但其在大肝癌细胞癌（HCC）中的功能及分子机制仍难以捉摸。本研究中，我们探讨了hsa_circ_0005785在HCC中的功能及其潜在机制，该环状RNA在HCC中异常高表达，并与HCC患者的TNM分期及总生存期相关。此外，hsa_circ_0005785的降解可抑制HCC细胞的增殖和转移，在体外诱导细胞凋亡和细胞周期停滞，并在体内抑制HCC细胞的生长。进一步机制分析揭示，hsa_circ_0005785通过充当miRNA海绵的作用吸附miR-578，导致增殖诱导配体（APRIL）及其mRNA靶标miR-578的表达解除抑制。此外，hsa_circ_0005785逆转了miR-578对HCC的抑制作用，并通过miR-578/APRIL轴加速肿瘤的恶性进展。综上所述，本研究揭示了hsa_circ_0005785在HCC肿瘤发生中的致癌作用。此外，针对hsa_circ_0005785/miR-578/APRIL调控通路可能成为HCC临床实践中的有前景的诊断和治疗策略。