Department of Pathology, The First Hospital, Jilin University, China.
Department of Radiology, The First Hospital, Jilin University, China.
Kaohsiung J Med Sci. 2019 Nov;35(11):659-671. doi: 10.1002/kjm2.12108. Epub 2019 Jul 22.
Prostate cancer (PCa) remains the secondary highest cause of cancer-related death in the United States in men. It has been reported that microRNAs can serve as key regulators in tumor development and progression in various cancers including PCa. In this study, we examined the effect of miR-498 on proliferation, radiosensitivity, invasion, and migration of PCa cells. The proliferation of LNCaP and DU-145 PCa cells with altered expression of miR-498 was evaluated by MTT assay. The invasion and migration of LNCaP and DU-145 PCa cells were assess by matrigel invasion assay and transwell migration assay. The protein expression level in PCa cells was examined by western blot. The function of miR-498 on radiation-induced apoptosis in LNCaP and DU-145 PCa cells was detected by Caspase-Glo3/7 assay. Forced expression of miR-498 improved the proliferation, invasion and migration in PCa cells. Furthermore, miR-498 decreased the sensitivity of PCa cells after ionizing radiation treatment. MiR-498 reduced the radiation-induced apoptosis in PCa cells by regulation of BAX and Bcl-2 expression. Meanwhile, miR-498 altered the expression of E-cadherin, N-cadherin, snail, and Vimentin in both LNCaP and DU-145 PCa cells and regulated epithelial to mesenchymal transition (EMT). Further study showed that aberrant expression of miR-498 changed the expression levels of phosphatase and tensin homolog and p-AKT in LNCaP and DU-145 PCa cells. In a summary, miR-498 displayed important roles in tumor development and progression in PCa cells, and might act as a potential prognostic biomarker and predict radiotherapy response in PCa.
前列腺癌(PCa)仍然是美国男性癌症相关死亡的第二大主要原因。据报道,microRNAs 可以作为多种癌症(包括 PCa)肿瘤发生和发展的关键调节因子。在这项研究中,我们研究了 miR-498 对 PCa 细胞增殖、放射敏感性、侵袭和迁移的影响。通过 MTT 分析评估改变 miR-498 表达的 LNCaP 和 DU-145 PCa 细胞的增殖。通过 Matrigel 侵袭分析和 Transwell 迁移分析评估 LNCaP 和 DU-145 PCa 细胞的侵袭和迁移。通过 Western blot 检测 PCa 细胞中的蛋白表达水平。通过 Caspase-Glo3/7 分析检测 miR-498 对 LNCaP 和 DU-145 PCa 细胞辐射诱导凋亡的功能。强制表达 miR-498 可改善 PCa 细胞的增殖、侵袭和迁移。此外,miR-498 降低了 PCa 细胞经电离辐射处理后的敏感性。miR-498 通过调节 BAX 和 Bcl-2 的表达减少了 PCa 细胞的辐射诱导凋亡。同时,miR-498 改变了 LNCaP 和 DU-145 PCa 细胞中 E-cadherin、N-cadherin、snail 和 Vimentin 的表达,并调节上皮间质转化(EMT)。进一步的研究表明,miR-498 异常表达改变了 LNCaP 和 DU-145 PCa 细胞中磷酸酶和张力蛋白同系物和 p-AKT 的表达水平。总之,miR-498 在 PCa 细胞的肿瘤发生和发展中发挥了重要作用,可能作为潜在的预后生物标志物预测 PCa 的放疗反应。