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顺铂耐药相关环状RNA_101237作为肝细胞癌的预后生物标志物。

Cisplatin resistance-associated circRNA_101237 serves as a prognostic biomarker in hepatocellular carcinoma.

作者信息

Zhou Shuping, Wei Juan, Wang Yeliu, Liu Xinkuang

机构信息

Department of Gastroenterology and Hepatology, Huainan First People's Hospital and First Affiliated Hospital of The Medical College of Anhui University of Science and Technology, Huainan, Anhui 232000, P.R. China.

出版信息

Exp Ther Med. 2020 Apr;19(4):2733-2740. doi: 10.3892/etm.2020.8526. Epub 2020 Feb 12.

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated mortality worldwide. Despite clinical advances, the survival rate of patients with HCC remains low, as most patients are diagnosed with HCC when they are already at the advanced stage. Certain circular RNAs (circRNAs) are closely associated with the development of liver cancer. In the present study, a circRNA array was performed to screen differentially expressed circRNAs in HCC tissues. The further analysis focused on the newly identified circRNA_101237, the host gene of which, cyclin-dependent kinase 8, is located at chr13:26974589-26975761. CircRNA_101237 was determined to be upregulated in tumor tissue and serum of patients with HCC as compared with that in paracancerous tissues and the serum of healthy controls, respectively. In addition, the expression of circRNA_101237 was associated with tumor size, lymph node metastasis, distant metastasis and TNM stage. Univariate and multivariate analysis indicated that serum circRNA_101237 levels were an independent predictor of survival prognosis in patients with HCC. The overall survival of patients with high expression of circRNA_101237 was reduced compared with that of patients with low expression of circRNA_101237. Of note, cisplatin induced the expression of circRNA_101237 in HCC cells in a dose- and time-dependent manner , and the levels of circRNA_101237 in the serum of patients with cisplatin-resistant HCC and in cisplatin-resistant Huh7 cells were increased. The present study provided novel insight into the use of circRNA_101237 as a diagnostic biomarker for HCC and a potential therapeutic target.

摘要

肝细胞癌(HCC)是全球癌症相关死亡的主要原因。尽管临床取得了进展,但HCC患者的生存率仍然很低,因为大多数患者在已经处于晚期时才被诊断出患有HCC。某些环状RNA(circRNA)与肝癌的发生密切相关。在本研究中,进行了circRNA阵列分析以筛选HCC组织中差异表达的circRNA。进一步的分析集中在新鉴定的circRNA_101237上,其宿主基因细胞周期蛋白依赖性激酶8位于chr13:26974589 - 26975761。与癌旁组织和健康对照血清相比,circRNA_101237在HCC患者的肿瘤组织和血清中分别被确定为上调。此外,circRNA_101237的表达与肿瘤大小、淋巴结转移、远处转移和TNM分期相关。单因素和多因素分析表明,血清circRNA_101237水平是HCC患者生存预后的独立预测指标。与circRNA_101237低表达患者相比,circRNA_101237高表达患者的总生存期缩短。值得注意的是,顺铂以剂量和时间依赖性方式诱导HCC细胞中circRNA_101237的表达,顺铂耐药HCC患者血清和顺铂耐药Huh7细胞中circRNA_101237的水平升高。本研究为circRNA_101237作为HCC的诊断生物标志物和潜在治疗靶点的应用提供了新的见解。

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本文引用的文献

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Recent advances in medical management of hepatocellular carcinoma.肝细胞癌医学管理的最新进展
Hepatol Res. 2019 Jan;49(1):14-32. doi: 10.1111/hepr.13259. Epub 2018 Dec 1.
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Non-coding RNA in drug resistance of hepatocellular carcinoma.非编码 RNA 在肝癌耐药中的作用。
Biosci Rep. 2018 Oct 9;38(5). doi: 10.1042/BSR20180915. Print 2018 Oct 31.
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Emerging role of long non-coding RNAs in cisplatin resistance.长链非编码RNA在顺铂耐药中的新作用。
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The Emerging Role of Circular RNAs in Hepatocellular Carcinoma.环状RNA在肝细胞癌中的新兴作用
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