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miR-193b-3p 通过靶向激活蛋白激酶 3 发挥抑制卵巢癌细胞肿瘤活性的作用。

miR-193b-3p possesses anti-tumor activity in ovarian carcinoma cells by targeting p21-activated kinase 3.

机构信息

Department of Obstetrics and Gynecology, Affiliated Hospital of Hebei University, Baoding, Hebei 071000, PR China.

Department of Obstetrics and Gynecology, Affiliated Hospital of Hebei University, Baoding, Hebei 071000, PR China.

出版信息

Biomed Pharmacother. 2017 Dec;96:1275-1282. doi: 10.1016/j.biopha.2017.11.086. Epub 2017 Nov 21.

Abstract

miR-193b-3p was found to be downregulated and contributed to ovarian cancer (OC) progression. In the present study, we aimed to study the detailed role of miR-193b-3p in the development of OC and the underlying molecular mechanism. The results showed that miR-193b-3p was downregulated while PAK3 was upregulated in OC cells. Ectopic expression of miR-193b-3p and PAK3 knockdown repressed cell proliferation, promoted paclitaxel-induced cytotoxicity, and reinforced paclitaxel-mediated caspase-3 activity increase in OC cells. Notably, miR-193b-3p was identified to directly target PAK3 and suppressed PAK3 expression. Moreover, enforced expression of PAK3 partially overturned the effects of miR-193b-3p on OC cell proliferation and paclitaxel sensitivity. In conclusion, miR-193b-3p possessed anti-tumor activity in OC through inhibiting cell proliferation and enhancing paclitaxel sensitivity by targeting PAK3. Therefore, our study suggested that the miR-193b-3p/PAK3 axis might be a potential novel therapeutic target for OC.

摘要

miR-193b-3p 被发现下调,并促进卵巢癌 (OC) 的进展。在本研究中,我们旨在研究 miR-193b-3p 在 OC 发展中的详细作用及其潜在的分子机制。结果表明,miR-193b-3p 在 OC 细胞中下调,而 PAK3 上调。miR-193b-3p 的过表达和 PAK3 的敲低抑制了 OC 细胞的增殖,促进了紫杉醇诱导的细胞毒性,并增强了紫杉醇介导的 caspase-3 活性增加。值得注意的是,miR-193b-3p 被鉴定为直接靶向 PAK3 并抑制 PAK3 表达。此外,PAK3 的强制表达部分推翻了 miR-193b-3p 对 OC 细胞增殖和紫杉醇敏感性的影响。总之,miR-193b-3p 通过靶向 PAK3 抑制细胞增殖和增强紫杉醇敏感性在 OC 中发挥抗肿瘤活性。因此,我们的研究表明,miR-193b-3p/PAK3 轴可能是 OC 的一个潜在的新的治疗靶点。

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