Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, 150081, China.
College of Medical Laboratory Science and Technology, Harbin Medical University (Daqing), Daqing, 163319, China.
Cell Death Dis. 2020 May 11;11(5):340. doi: 10.1038/s41419-020-2532-y.
Circular RNAs (circRNAs) are a class of non-coding RNAs with a loop structure; however, their functions remain largely unknown. Growing evidence suggests that circRNAs play a pivotal role in the progression of malignant diseases. However, the expression profiles and function of circRNAs in hepatocellular carcinoma (HCC) remain unclear. We investigated the expression of microtubule-associated serine/threonine kinase 1 (MAST1) circRNA (circMAST1) in HCC and healthy tissues using bioinformatics, quantitative real-time PCR (qRT-PCR), and fluorescence in situ hybridization. Luciferase reporter assays were performed to assess the interaction between circMAST1 and miR-1299. Proliferation assays, colony formation assays, flow cytometry, transwell assays, and western blotting were also performed. A mouse xenograft model was also used to determine the effect of circMAST1 on HCC growth in vivo. CircMAST1 was upregulated in HCC tissues and cell lines; silencing via small interfering RNA inhibited migration, invasion, and proliferation of HCC cell lines in vitro as well as tumor growth in vivo. Furthermore, the expression of circMAST1 was positively correlated with catenin delta-1 (CTNND1) and negatively correlated with microRNA (miR)-1299 in HCC clinical samples. Importantly, circMAST1 sponged miR-1299 to stabilize the expression of CTNND1 and promoted tumorigenic features in HCC cell lines. We found that circMAST1 may serve as a novel biomarker for HCC. Moreover, circMAST1 elicits HCC progression by sponging miRNA-1299 and stabilizing CTNND1. Our data provide potential options for therapeutic targets in patients with HCC.
环状 RNA（circRNAs）是一类具有环状结构的非编码 RNA，但它们的功能仍知之甚少。越来越多的证据表明，circRNAs 在恶性疾病的进展中起着关键作用。然而，circRNAs 在肝细胞癌（HCC）中的表达谱和功能仍不清楚。我们使用生物信息学、实时定量 PCR（qRT-PCR）和荧光原位杂交技术研究了 HCC 和正常组织中微管相关丝氨酸/苏氨酸激酶 1（MAST1）circRNA（circMAST1）的表达。通过荧光素酶报告基因检测评估了 circMAST1 与 miR-1299 之间的相互作用。还进行了增殖实验、集落形成实验、流式细胞术、Transwell 实验和 Western blot 实验。还建立了小鼠异种移植模型，以确定 circMAST1 在体内对 HCC 生长的影响。circMAST1 在 HCC 组织和细胞系中上调；通过小干扰 RNA 沉默可抑制 HCC 细胞系在体外的迁移、侵袭和增殖以及体内肿瘤生长。此外，circMAST1 的表达与 HCC 临床样本中的连环蛋白 delta-1（CTNND1）呈正相关，与 microRNA（miR）-1299 呈负相关。重要的是，circMAST1 作为 miR-1299 的海绵，稳定了 CTNND1 的表达，并促进了 HCC 细胞系的致瘤特征。我们发现 circMAST1 可能是 HCC 的一种新型生物标志物。此外，circMAST1 通过海绵吸附 miRNA-1299 和稳定 CTNND1 来引发 HCC 进展。我们的数据为 HCC 患者的治疗靶点提供了潜在的选择。
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