Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, 180 Fenglin Road, Shanghai, 200032, People's Republic of China.
Cancer Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200031, People's Republic of China.
Mol Cancer. 2019 Jun 1;18(1):105. doi: 10.1186/s12943-019-1031-1.
Recently, the dysregulation of circular RNA (circRNA) have been shown to have important regulatory roles in cancer development and progression, including hepatocellular carcinoma (HCC). However, the roles of most circRNAs in HCC are still unknown.
The expression of circular tripartite motif containing 33-12 (circTRIM33-12) in HCC tissues and cell lines was detected by qRT-PCR. The role of circTRIM33-12 in HCC progression was assessed by western blotting, CCK-8, flow cytometry, transwell and a subcutaneous tumor mouse assays both in vitro and in vivo. In vivo circRNA precipitation, RNA immunoprecipitation, luciferase reporter assays were performed to evaluate the interaction between circTRIM33-12 and miR-191.
Here, we found that circTRIM33-12, is downregulated in HCC tissues and cell lines. The downregulation of circTRIM33-12 in HCC was significantly correlated with malignant characteristics and served as an independent risk factor for the overall survival (OS) and recurrence-free survival (RFS) of patients with HCC after surgery. The reduced expression of circTRIM33-12 in HCC cells increases tumor proliferation, migration, invasion and immune evasion. Mechanistically, we demonstrated that circTRIM33-12 upregulated TET1 expression by sponging miR-191, resulting in significantly reduced 5-hydroxymethylcytosine (5hmC) levels in HCC cells.
These results reveal the important role of circTRIM33-12 in the proliferation, migration, invasion and immune evasion abilities of HCC cells and provide a new perspective on circRNAs in HCC progression.
最近的研究表明，环状 RNA（circRNA）的失调在癌症的发展和进展中具有重要的调节作用，包括肝细胞癌（HCC）。然而，大多数 circRNA 在 HCC 中的作用仍然未知。
通过 qRT-PCR 检测 HCC 组织和细胞系中环状三肽重复蛋白 33-12（circTRIM33-12）的表达。通过 Western blot、CCK-8、流式细胞术、transwell 和皮下肿瘤小鼠实验，在体外和体内评估 circTRIM33-12 在 HCC 进展中的作用。进行体内 circRNA 沉淀、RNA 免疫沉淀、荧光素酶报告基因实验，以评估 circTRIM33-12 与 miR-191 之间的相互作用。
我们发现，circTRIM33-12 在 HCC 组织和细胞系中下调。circTRIM33-12 在 HCC 中的下调与恶性特征显著相关，并作为 HCC 患者手术后总生存期（OS）和无复发生存期（RFS）的独立危险因素。HCC 细胞中 circTRIM33-12 的表达减少会增加肿瘤的增殖、迁移、侵袭和免疫逃逸。机制上，我们证明 circTRIM33-12 通过海绵吸附 miR-191 而上调 TET1 的表达，导致 HCC 细胞中的 5-羟甲基胞嘧啶（5hmC）水平显著降低。
这些结果揭示了 circTRIM33-12 在 HCC 细胞增殖、迁移、侵袭和免疫逃逸能力中的重要作用，并为 circRNAs 在 HCC 进展中的作用提供了新的视角。
