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环状RNA_101505通过吸附miR-103使肝癌细胞对顺铂敏感,并促进含氧化还原硝基结构域蛋白1的表达。

CircRNA_101505 sensitizes hepatocellular carcinoma cells to cisplatin by sponging miR-103 and promotes oxidored-nitro domain-containing protein 1 expression.

作者信息

Luo Yanwei, Fu Yunfeng, Huang Rong, Gao Meng, Liu Fengxia, Gui Rong, Nie Xinmin

机构信息

Department of Blood Transfusion, the Third Xiangya Hospital of Central South University, Tongzipo Road 138, 410013 Changsha, China.

出版信息

Cell Death Discov. 2019 Jul 29;5:121. doi: 10.1038/s41420-019-0202-6. eCollection 2019.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and a leading cause of cancer-related deaths worldwide. Emerging studies have shown that circular RNAs (circRNAs) are differentially expressed in HCC and play an important role in HCC pathogenesis and metastasis. However, the mechanism of circRNA in the chemoresistance of HCC remains unclear. In this study, we aimed to investigate the role of circRNA in cisplatin resistance of HCC. We identified a novel circRNA circRNA_101505 that was decreased in cisplatin-resistant HCC tissues and cell lines, and associated with a poor survival outcome. Gain-of-function investigations showed that overexpression of circRNA_101505 suppressed cancer cell growth in vivo and in vitro, and enhanced cisplatin toxicity in HCC cells. Mechanistic studies found that circRNA_101505 could sensitize HCC cells to cisplatin by sponging miR-103, and thereby promoting oxidored-nitro domain-containing protein 1 (NOR1) expression. In conclusion, the significant inhibitory effects indicate circRNA_101505 to be a potential therapeutic target for HCC treatment. Our findings provide significant evidence to further elucidate the therapeutic use of circRNA in HCC.

摘要

肝细胞癌(HCC)是最常见的恶性肿瘤之一,也是全球癌症相关死亡的主要原因。新兴研究表明,环状RNA(circRNA)在HCC中存在差异表达,并在HCC的发病机制和转移中发挥重要作用。然而,circRNA在HCC化疗耐药中的机制仍不清楚。在本研究中,我们旨在探讨circRNA在HCC顺铂耐药中的作用。我们鉴定出一种新型circRNA circRNA_101505,其在顺铂耐药的HCC组织和细胞系中表达降低,并与不良生存结果相关。功能获得性研究表明,circRNA_101505的过表达在体内和体外均抑制癌细胞生长,并增强HCC细胞对顺铂的毒性。机制研究发现,circRNA_101505可通过吸附miR-103使HCC细胞对顺铂敏感,从而促进含氧化还原-硝基结构域蛋白1(NOR1)的表达。总之,显著的抑制作用表明circRNA_101505是HCC治疗的潜在靶点。我们的研究结果为进一步阐明circRNA在HCC治疗中的应用提供了重要证据。

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