Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, Hubei, P.R. China.
J Exp Clin Cancer Res. 2021 Feb 4;40(1):57. doi: 10.1186/s13046-021-01861-6.
Hepatocellular carcinoma (HCC) is a common type of malignant human cancer with high morbidity and poor prognosis, causing numerous deaths per year worldwide. Growing evidence has been demonstrated that long non-coding RNAs (lncRNAs) are closely associated with hepatocarcinogenesis and metastasis. However, the roles, functions, and working mechanisms of most lncRNAs in HCC remain poorly defined.
Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression level of CCDC183-AS1 in HCC tissues and cell lines. Cell proliferation, migration and invasion ability were evaluated by CCK-8 and transwell assay, respectively. Animal experiments were used to explore the role of CCDC183-AS1 and miR-589-5p in vivo. Bioinformatic analysis, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to confirm the regulatory relationship between CCDC183-AS1, miR-589-5p and SKP1.
Significantly upregulated expression of CCDC183-AS1 was observed in both HCC tissues and cell lines. HCC patients with higher expression of CCDC183-AS1 had a poorer overall survival rate. Functionally, overexpression of CCDC183-AS1 markedly promoted HCC cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo, whereas the downregulation of CCDC183-AS1 exerted opposite effects. MiR-589-5p inhibitor counteracted the proliferation, migration and invasion inhibitory effects induced by CCDC183-AS1 silencing. Mechanistically, CCDC183-AS1 acted as a ceRNA through sponging miR-589-5p to offset its inhibitory effect on the target gene SKP1, then promoted the tumorigenesis of HCC.
CCDC183-AS1 functions as an oncogene to promote HCC progression through the CCDC183-AS1/miR-589-5p/SKP1 axis. Our study provided a novel potential therapeutic target for HCC patients.
肝细胞癌(HCC)是一种常见的人类恶性肿瘤,发病率高,预后差,每年在全球范围内导致大量死亡。越来越多的证据表明,长链非编码 RNA(lncRNA)与肝癌的发生和转移密切相关。然而,大多数 lncRNA 在 HCC 中的作用、功能和作用机制仍未得到明确界定。
实时定量聚合酶链反应(qRT-PCR)检测 HCC 组织和细胞系中 CCDC183-AS1 的表达水平。CCK-8 法和 Transwell 实验分别评估细胞增殖、迁移和侵袭能力。动物实验用于研究 CCDC183-AS1 和 miR-589-5p 在体内的作用。生物信息学分析、双荧光素酶报告基因实验和 RNA 免疫沉淀(RIP)实验证实了 CCDC183-AS1、miR-589-5p 和 SKP1 之间的调控关系。
CCDC183-AS1 在 HCC 组织和细胞系中均呈显著上调表达。CCDC183-AS1 表达较高的 HCC 患者总生存率较低。功能上,CCDC183-AS1 过表达显著促进 HCC 细胞体外增殖、迁移和侵袭,体内肿瘤生长和转移,而 CCDC183-AS1 下调则产生相反的效果。CCDC183-AS1 沉默诱导的增殖、迁移和侵袭抑制作用被 miR-589-5p 抑制剂逆转。机制上,CCDC183-AS1 通过海绵吸附 miR-589-5p 作为 ceRNA 来抵消其对靶基因 SKP1 的抑制作用,从而促进 HCC 的发生。
CCDC183-AS1 通过 CCDC183-AS1/miR-589-5p/SKP1 轴发挥癌基因作用,促进 HCC 进展。本研究为 HCC 患者提供了一个新的潜在治疗靶点。