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微小RNA-219-5p通过靶向Twist/Wnt/β-连环蛋白信号通路抑制上皮性卵巢癌细胞的增殖、迁移和侵袭。

MicroRNA-219-5p inhibits the proliferation, migration, and invasion of epithelial ovarian cancer cells by targeting the Twist/Wnt/β-catenin signaling pathway.

作者信息

Wei Chunyan, Zhang Xi, He Sai, Liu Bianli, Han Hongfang, Sun Xuejun

机构信息

Department of Gynaecology and Obstetrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.

Department of Neurosurgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.

出版信息

Gene. 2017 Dec 30;637:25-32. doi: 10.1016/j.gene.2017.09.012. Epub 2017 Sep 7.

Abstract

MicroRNAs are emerging as critical regulators in various fundamental biological processes, including tumor progression. MicroRNA-219-5p (miR-219-5p) has been suggested as a novel tumor suppressing miRNA for many types of human cancers. However, the expression and functional significance of miR-219-5p in epithelial ovarian cancer remain poorly understood. In this study, we sought to explore the potential functions of miR-219-5p in epithelial ovarian cancer. Herein, we found that miR-219-5p levels were significantly decreased in epithelial ovarian cancer tissues and cell lines. Further experiments showed that overexpression of miR-219-5p inhibited epithelial ovarian cancer cell proliferation, migration, and invasion, and suppressed the Wnt/β-catenin signaling pathway. By contrast, suppression of miR-219-5p exhibited the opposite effects. Twist was identified as a downstream target of miR-219-5p, and its expression was directly regulated by miR-219-5p. Restoration of Twist expression in miR-219-5p-overexpresing cells significantly reversed the antitumor effects of miR-219-5p. Taken together, our results revealed a tumor suppressive role for miR-219-5p in epithelial ovarian cancer that includes suppression of cell proliferation, migration, and invasion through downregulation of the Twist/Wnt/β-catenin signaling pathway. Our study suggests that miR-219-5p may have potential applications in the diagnosis and treatment of epithelial ovarian cancer.

摘要

微小RNA正成为包括肿瘤进展在内的各种基本生物学过程中的关键调节因子。微小RNA - 219 - 5p(miR - 219 - 5p)已被认为是多种人类癌症的新型肿瘤抑制性微小RNA。然而,miR - 219 - 5p在上皮性卵巢癌中的表达及功能意义仍知之甚少。在本研究中,我们试图探索miR - 219 - 5p在上皮性卵巢癌中的潜在功能。在此,我们发现上皮性卵巢癌组织和细胞系中miR - 219 - 5p水平显著降低。进一步实验表明,miR - 219 - 5p的过表达抑制上皮性卵巢癌细胞的增殖、迁移和侵袭,并抑制Wnt/β - 连环蛋白信号通路。相反,抑制miR - 219 - 5p则表现出相反的效果。Twist被确定为miR - 219 - 5p的下游靶点,其表达直接受miR - 219 - 5p调控。在miR - 219 - 5p过表达细胞中恢复Twist表达可显著逆转miR - 219 - 5p的抗肿瘤作用。综上所述,我们的结果揭示了miR - 219 - 5p在上皮性卵巢癌中的肿瘤抑制作用,包括通过下调Twist/Wnt/β - 连环蛋白信号通路来抑制细胞增殖、迁移和侵袭。我们的研究表明,miR - 219 - 5p可能在上皮性卵巢癌的诊断和治疗中具有潜在应用价值。

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