MicroRNA-144 Suppresses Prostate Cancer Growth and Metastasis by Targeting EZH2.
MicroRNA-144 Suppresses Prostate Cancer Growth and Metastasis by Targeting EZH2.
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DOI：
10.1177/1533033821989817
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发表时间：
2021-01
影响因子：
2.8
通讯作者：
Huang L
中科院分区：
文献类型：
--
作者：
Sun XB;Chen YW;Yao QS;Chen XH;He M;Chen CB;Yang Y;Gong XX;Huang L
前列腺癌是常见的恶性肿瘤，发病率较高。MicroRNAs(MiRNAs)已被证明是肿瘤发生过程中重要的转录后调节因子。本研究旨在探讨miR-144对前列腺癌增殖和凋亡的影响。检测临床PCa组织中miR-144和EZH2的表达。以PCa细胞系LNCaP和DU-145为研究对象，将miR-144模拟物或抑制剂导入PCa细胞系。通过荧光素酶报告基因检测，验证miR-144与EZH2的相关性。用CCK-8、流式细胞仪和创面愈合实验检测细胞存活率、细胞凋亡率和迁移能力。免疫印迹法检测EZH2、E-钙粘附素、N-钙粘附素和波形蛋白的蛋白表达水平。MIR-144与EZH2在PCa组织中的表达呈负相关。进一步研究发现，EZH2是miR-144的直接靶点。此外，miR-144过表达下调了EZH2的表达，降低了细胞存活率，促进了细胞凋亡，而miR-144过表达则导致相反的结果。MIR-144还抑制了PCa细胞上皮向间充质转化的水平。我们的研究表明，miR-144负性调节EZH2在临床标本和体外的表达。MIR-144对PCa细胞具有抑制增殖和诱导细胞凋亡的作用。因此，miR-144有可能作为预测PCa进展的生物标志物。
Prostate cancer is a common malignant tumor with a high incidence. MicroRNAs (miRNAs) have been shown to be important post-transcriptional regulators during tumorigenesis. This study aimed to explore the effect of miR-144 on PCa proliferation and apoptosis. The expression of miR-144 and EZH2 were examined in clinical PCa tissues. PCa cell line LNCAP and DU-145 was employed and transfected with miR-144 mimics or inhibitors. The correlation between miR-144 and EZH2 was verified by luciferase reporter assay. Cell viability, apoptosis and migratory capacity were detected by CCK-8, flow cytometry assay and wound healing assay. The protein level of EZH2, E-Cadherin, N-Cadherin and vimentin were analyzed by western blotting. miR-144 was found to be negatively correlated to the expression of EZH2 in PCa tissues. Further studies identified EZH2 as a direct target of miR-144. Moreover, overexpression of miR-144 downregulated expression of EZH2, reduced cell viability and promoted cell apoptosis, while knockdown of miR-144 led to an inverse result. miR-144 also suppressed epithelial-mesenchymal transition level of PCa cells. Our study indicated that miR-144 negatively regulate the expression of EZH2 in clinical specimens and in vitro. miR-144 can inhibit cell proliferation and induce cell apoptosis in PCa cells. Therefore, miR-144 has the potential to be used as a biomarker for predicting the progression of PCa.
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