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MicroRNA-664 suppresses the growth of cervical cancer cells via targeting c-Kit

机译:MicroRNA-664通过靶向c-Kit抑制宫颈癌细胞的生长

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Background: Cervical cancer is the second most common malignant cancer in women worldwide. Evidence indicated that miR-664 was significantly downregulated in cervical cancer. However, the mechanisms by which miR-664 regulates the tumorigenesis of cervical cancer remain unclear. Thus, this study aimed to investigate the role of miR-664 in cervical cancer. Methods: Quantitative reverse transcription polymerase chain reaction was used to detect the level of miR-664 in tumor tissues and cell line. The dual luciferase reporter system assay and Western blotting were used to explore the interaction of miR-664 and c-Kit in cervical cancer. Results: The expression of miR-664 in patients with cervical cancer was dramatically decreased compared with that in adjacent tissues. MiR-664 mimics significantly inhibited proliferation in SiHa cells via inducing apoptosis. In addition, miR-664 mimics induced apoptosis in SiHa cells via increasing the expressions of Bax and active caspase 3 and decreasing the level of Bcl-2. Moreover, dual-luciferase assay showed that c-Kit was the directly binding target of miR-664 in SiHa cells; overexpression of miR-664 downregulated the expression of c-Kit. Meanwhile, upregulation of miR-664 significantly decreased the levels of c-Myc and Cyclin D in cells. Furthermore, miR-664 markedly inhibited tumor growth of cervical cancer in xenograft. Conclusion: Our data indicated that miR-664 exerted antitumor effects on SiHa cells by directly targeting c-Kit in vitro and in vivo. Therefore, miR-664 might be a potential therapeutic target for the treatment of patients with cervical cancer.
机译:背景:宫颈癌是全世界女性中第二大最常见的恶性肿瘤。有证据表明,miR-664在宫颈癌中显着下调。但是,miR-664调节子宫颈癌的发生机制尚不清楚。因此,本研究旨在研究miR-664在宫颈癌中的作用。方法:采用定量逆转录聚合酶链反应检测肿瘤组织和细胞株中miR-664的水平。双重荧光素酶报告系统分析和Western印迹用于探讨miR-664和c-Kit在宫颈癌中的相互作用。结果:与癌旁组织相比,宫颈癌患者miR-664的表达明显降低。 MiR-664模拟物通过诱导凋亡显着抑制SiHa细胞的增殖。另外,miR-664模拟物通过增加Bax和活性caspase 3的表达并降低Bcl-2的水平来诱导SiHa细胞凋亡。此外,双荧光素酶测定法表明,c-Kit是miR-664在SiHa细胞中的直接结合靶标。 miR-664的过表达下调了c-Kit的表达。同时,miR-664的上调显着降低了细胞中c-Myc和Cyclin D的水平。此外,miR-664显着抑制异种移植中子宫颈癌的肿瘤生长。结论:我们的数据表明,miR-664通过直接靶向c-Kit在体内和体外对SiHa细胞发挥抗肿瘤作用。因此,miR-664可能是治疗宫颈癌患者的潜在治疗靶标。

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