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长链非编码 RNA CCDC183-AS1 通过调控 SKP1 表达作为 miR-589-5p 的海绵促进肝癌的进展。

Long non-coding RNA CCDC183-AS1 acts AS a miR-589-5p sponge to promote the progression of hepatocellular carcinoma through regulating SKP1 expression.

机构信息

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.

出版信息

J Exp Clin Cancer Res. 2021 Feb 4;40(1):57. doi: 10.1186/s13046-021-01861-6.

DOI:10.1186/s13046-021-01861-6
PMID:33541391
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7863448/
Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

背景

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。

方法

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。

结果

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。

结论

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7376/7863448/2834082f9ab1/13046_2021_1861_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7376/7863448/2834082f9ab1/13046_2021_1861_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7376/7863448/fadeeb12af78/13046_2021_1861_Fig1_HTML.jpg
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