Transcriptional activation of miR-320a by ATF2, ELK1 and YY1 induces cancer cell apoptosis under ionizing radiation conditions
Transcriptional activation of miR-320a by ATF2, ELK1 and YY1 induces cancer cell apoptosis under ionizing radiation conditions
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ATF2、ELK1 和 YY1 转录激活 miR-320a 诱导电离辐射条件下癌细胞凋亡
DOI：
10.3892/ijo.2018.4497
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发表时间：
2018-10-01
影响因子：
5.2
通讯作者：
Zheng, Xiaofei
中科院分区：
文献类型：
--
作者：
Hu, Zheng;Tie, Yi;Zheng, Xiaofei
microRNA（miRNAs或miRs）在许多细胞过程中发挥重要作用，包括发育、增殖、肿瘤发生和凋亡。已有研究表明，电离辐射（IR）可诱导癌细胞中miRNA的表达。然而，潜在的分子机制尚未完全理解。在这项研究中，内源性miR-320 a及其主要前体（pri-miR-320 a）通过逆转录-定量PCR（RT-qPCR）进行测定。使用双荧光素酶报告基因测定系统测量荧光素酶活性。Western blot分析miR-320 a上下游基因的蛋白表达。Annexin V凋亡检测法检测细胞凋亡，台盼蓝拒染法检测细胞增殖。结果显示，miR-320 a的表达随IR剂量和治疗持续时间线性增加。在IR条件下，p38丝裂原活化蛋白激酶（MAPK）和丝裂原活化蛋白激酶8（JNK）以及上调的miR-320 a表达激活了三种转录因子，即转录激活因子2（ATF 2）、ETS转录因子（ELK 1）和YY 1转录因子（YY 1）。此外，还鉴定了X连锁凋亡抑制因子（XIAP）是IR反应期间的miR-320 a靶基因。miR-320 a通过靶向XIAP诱导肿瘤细胞凋亡并抑制肿瘤细胞增殖。总体而言，本研究的结果表明，miRNA-320 a受p38 MAPK/JNK通路的调节，通过抑制XIAP增强癌细胞的放射敏感性，因此这可能被证明是一种潜在的治疗方法，用于克服癌症治疗中的放射抗性。
MicroRNAs (miRNAs or miRs) play important roles in numerous cellular processes, including development, proliferation, tumorigenesis and apoptosis. It has been reported that miRNA expression is induced by ionizing radiation (IR) in cancer cells. However, the underlying molecular mechanisms are not yet fully understood. In this study, endogenous miR-320a and its primary precursor (pri-miR-320a) were assayed by reverse transcription-quantitative PCR (RT-qPCR). Luciferase activities were measured using a dual-luciferase reporter assay system. Western blot analysis was used to determine the protein expressions of upstream and downstream genes of miR-320a. Cell apoptosis was evaluated by Annexin V apoptosis assay and cell proliferation was measured using the trypan blue exclusion method. The results revealed that miR-320a expression increased linearly with the IR dose and treatment duration. Three transcription factors, activating transcription factor 2 (ATF2), ETS transcription factor (ELK1) and YY1 transcription factor (YY1), were activated by p38 mitogen-activated protein kinase (MAPK) and mitogen-activated protein kinase 8 (JNK) and by upregulated miR-320a expression under IR conditions. In addition, it was identified that X-linked inhibitor of apoptosis (XIAP) was an miR-320a target gene during the IR response. By targeting XIAP, miR-320a induced apoptosis and inhibited the proliferation of the cancer cells. On the whole, the results of this study demonstrated that miRNA-320a, regulated by the p38 MAPK/JNK pathway, enhanced the radiosensitivity of cancer cells by inhibiting XIAP and this may thus prove to be a potential therapeutic approach with which to overcome radioresistance in cancer treatment.