Institute for Translational Medicine, Qingdao University, Qingdao 266021, China.
Henan Key Laboratory of Cancer Epigenetics, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China.
Int J Med Sci. 2020 May 30;17(10):1351-1365. doi: 10.7150/ijms.45637. eCollection 2020.
Liver cancer is one of the most common malignant tumors in the world. Circular RNAs (circRNAs) perform important functions in cancer progression and are regarded as prospective biomarkers for cancer diagnosis and therapy. Here, we used the high-throughput RNA sequencing technology in conjunction with bioinformatics tools to profile circRNA expression in patients with HBV-related liver cancer. A total of 13,124 circRNAs were identified in HBV-related liver cancer, approximately 86.25% of which were sense-overlapping circRNAs. Moreover, 2,996 circRNAs exhibited different expression patterns between liver cancer tissues and matched pericancerous tissues. Function annotation indicated that these aberrantly expressed circRNAs were primarily engaged in cellular processes and cancer-associated pathways. Notably, the circRNA-miRNA interaction networks showed that 6,020 circRNAs were predicted to target 1,654 miRNAs. Quantitative RT-PCR (qRT-PCR) assay indicated that ten randomly selected circRNAs displayed consistent expression patterns with the sequencing results. We further predicted that circRNA_10156 might work as a molecular sponge of miR-149-3p, which served an important function in tumor development. Consequently, our results demonstrated that depletion of circRNA_10156 upregulated miR-149-3p, reduced Akt1 expression, and suppressed liver cancer cell proliferation. The present study will facilitate the elucidation of biological functions of circRNAs in the progression of HBV-related liver cancer providing prospective biomarkers and therapeutic targets for this disease. Our findings also reveal that circRNA_10156 might represent a promising therapeutic target for liver cancer management.
肝癌是世界上最常见的恶性肿瘤之一。环状 RNA(circRNAs)在癌症进展中发挥着重要作用,被认为是癌症诊断和治疗的有前途的生物标志物。在这里,我们使用高通量 RNA 测序技术结合生物信息学工具来描绘 HBV 相关肝癌患者的 circRNA 表达谱。在 HBV 相关肝癌中鉴定出了 13124 个 circRNA,其中约 86.25%为顺式重叠 circRNA。此外,肝癌组织与配对癌旁组织之间有 2996 个 circRNA 表现出不同的表达模式。功能注释表明,这些异常表达的 circRNA 主要参与细胞过程和癌症相关途径。值得注意的是,circRNA-miRNA 相互作用网络表明 6020 个 circRNA 被预测靶向 1654 个 miRNA。定量 RT-PCR(qRT-PCR)检测表明,随机选择的 10 个 circRNA 与测序结果具有一致的表达模式。我们进一步预测 circRNA_10156 可能作为 miR-149-3p 的分子海绵发挥作用,后者在肿瘤发展中起重要作用。因此,我们的结果表明,circRNA_10156 的缺失上调了 miR-149-3p,降低了 Akt1 的表达,并抑制了肝癌细胞的增殖。本研究将有助于阐明 circRNAs 在 HBV 相关肝癌进展中的生物学功能,为该疾病提供有前途的生物标志物和治疗靶点。我们的研究结果还表明,circRNA_10156 可能是肝癌治疗的一个有前途的靶点。