MicroRNA-621 Acts as a Tumor Radiosensitizer by Directly Targeting SETDB1 in Hepatocellular Carcinoma
MicroRNA-621 Acts as a Tumor Radiosensitizer by Directly Targeting SETDB1 in Hepatocellular Carcinoma
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MicroRNA-621 通过直接靶向肝细胞癌中的 SETDB1 作为肿瘤放射增敏剂
DOI：
10.1016/j.ymthe.2018.11.005
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发表时间：
2019-02-06
影响因子：
12.4
通讯作者：
Jiang, Jingting
中科院分区：
文献类型：
--
作者：
Shao, Yingjie;Song, Xing;Jiang, Jingting
放射治疗是肿瘤最重要的治疗手段之一。然而，由于正常肝细胞对放射的耐受性低，以及肝癌固有的放射抵抗性，放射治疗在肝癌中的应用受到限制。随着microRNAs（miRNAs）在肿瘤治疗中的研究不断深入，miRNAs对肿瘤放射敏感性的调控成为近年来的研究热点。在本研究中，miR-621在HCC组织和细胞中的表达较低，并且这种miR-621的低表达与HCC患者的不良预后相关。此外，体内外实验证实miR-621的高表达可显著增强肝癌的放射敏感性。肝癌组织中miR-621和SETDB 1的表达呈负相关。双荧光素酶报告基因检测表明miR-621可以直接靶向SETDB 1的3' UTR。此外，miR-621通过直接抑制SETDB 1而增强HCC细胞的放射敏感性。此外，miR-621和/或SETDB 1轴通过激活p53信号通路提高肝癌细胞的放射敏感性。综上所述，miR-621和/或SETDB 1可能被用作治疗HCC的新的治疗靶点。
Radiotherapy is one of the most important treatment methods of tumors. However, the application of radiotherapy in hepatocellular carcinoma (HCC) is limited due to the low tolerance of normal liver cells for radiation and inherent radiation resistance in HCC. With the in-depth study of microRNAs (miRNAs) in tumor therapy, the regulation of tumor radiosensitivity by miRNAs has been a research hotspot in recent years. In the present study, the expression of miR-621 was lower in HCC tissues and cells, and such low expression of miR-621 was associated with poor prognosis in HCC patients. In addition, in vivo and in vitro assays confirmed that the high expression of miR-621 could significantly enhance the radiosensitivity of HCC. Moreover, the expressions of miR-621 and SETDB1 in HCC tissues were negatively correlated. Dual-luciferase reporter assays indicated that miR-621 could directly target the 3' UTR of SETDB1. In addition, miR-621 enhanced the radiosensitivity of HCC cells via directly inhibiting SETDB1. Besides, the miR-621 and/or SETDB1 axis improved the radiosensitivity of HCC cells via activating the p53-signaling pathway. Taken together, miR-621 and/or SETDB1 might be used as a novel therapeutic target for the treatment of HCC.