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miR-30d-5p 通过靶向 NT5E 抑制前列腺癌细胞增殖和迁移的肿瘤抑制功能。

Tumor-Suppressive Function of miR-30d-5p in Prostate Cancer Cell Proliferation and Migration by Targeting NT5E.

机构信息

Department of Urology, Renmin Hospital of Wuhan University , Wuhan, China .

出版信息

Cancer Biother Radiopharm. 2018 Jun;33(5):203-211. doi: 10.1089/cbr.2018.2457.

Abstract

MiR-30d-5p, a member of the microRNA family, was recently reported to regulate androgen receptor signaling in prostate cancer (PCa). Ecto-5'-nucleotidase (NT5E/CD73) is a pivotal regulator of tumor migration and has angiogenetic properties. However, the undiscovered function of miR-30d-5p and whether it targeted NT5E in PCa remain uncertain. In this study, the authors observed miR-30d-5p was significantly downregulated in PCa tissues and cell lines compared with the adjacent normal tissues and normal prostate cells, respectively. The lower expression of miR-30d-5p was found to be inversely correlated with the NT5E expression in PCa tissues. Subsequently, the biological function of miR-30d-5p was evaluated in PCa in vitro. The results indicated that miR-30d-5p overexpression inhibited PCa cell growth and invasion by MTT, Transwell assays, respectively, as well as induced cell cycle G0/G1 phase arrest and apoptosis using flow cytometry analysis. In addition, miR-30d-5p directly bound to the 3'UTR (3' untranslated region) of NT5E in DU-145 and PC-3 cells by luciferase reporter assay. Furthermore, enforced NT5E expression alleviated miR-30d-5p inhibition of PCa cell growth and invasion in DU145 cells. Taken together, these data indicated that miR-30d-5p may be a potential therapeutic target for the treatment of PCa by serving as a tumor suppressor, by negatively regulating NT5E.

摘要

miR-30d-5p 是 microRNA 家族的一员,最近有研究报道其可调节前列腺癌(PCa)中的雄激素受体信号。外核苷酸酶(NT5E/CD73)是肿瘤迁移的关键调节因子,具有血管生成特性。然而,miR-30d-5p 的未知功能及其是否在 PCa 中靶向 NT5E 仍不确定。在本研究中,作者观察到 miR-30d-5p 在 PCa 组织和细胞系中的表达明显低于相邻正常组织和正常前列腺细胞。miR-30d-5p 的低表达与 PCa 组织中的 NT5E 表达呈负相关。随后,作者在体外评估了 miR-30d-5p 在 PCa 中的生物学功能。结果表明,miR-30d-5p 的过表达通过 MTT、Transwell 分析分别抑制了 PCa 细胞的生长和侵袭,并通过流式细胞术分析诱导了细胞周期 G0/G1 期阻滞和细胞凋亡。此外,通过荧光素酶报告基因检测,miR-30d-5p 直接与 DU-145 和 PC-3 细胞中的 NT5E 3'UTR(3'非翻译区)结合。此外,强制表达 NT5E 可减轻 miR-30d-5p 对 DU145 细胞中 PCa 细胞生长和侵袭的抑制作用。综上所述,这些数据表明,miR-30d-5p 可能通过负向调节 NT5E 作为肿瘤抑制因子,成为治疗 PCa 的潜在治疗靶点。

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