Department of Medical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.
J Cell Physiol. 2019 Feb;234(2):1827-1841. doi: 10.1002/jcp.27056. Epub 2018 Sep 7.
Breast cancer remains one of the foremost primary causes of female morbidity and mortality worldwide. During the current study, the effect of miR-590-5p and paired-like homeodomain transcription factor 2 (PITX2) on proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) of human breast cancer via the Wnt-β-catenin signaling pathway was investigated. Breast cancer-related genes and related signaling pathways were obtained from KEGG database. The PITX2 regulatory microRNA was predicted. To define the contributory role by which miR-590-5p influences the progression of breast cancer, the interaction between miR-590-5p and PITX2 was explored; the proliferation, invasion, and migration abilities as well as the tumor growth and metastasis in nude mice were detected following the overexpression or silencing of miR-590-5p. PITX2 was determined to share a correlation with breast cancer and miR-590-5p was selected for further analysis. PITX2, Wnt-1, β-catenin, N-cadherin, and vimentin all displayed higher levels, while miR-590-5p and E-cadherin expression were lower among breast cancer tissues than in the adjacent normal tissue. After overexpression of miR-590-5p or si-PITX2, the expression of E-cadherin was markedly increased, decreases in the expression of Wnt-1, β-catenin, N-cadherin, and vimentin, as well as inhibited cell proliferation, invasion, migration, metastasis, and EMT were observed. This study provides evidence suggesting that the transfection of overexpressed miR-590-5p can act to alleviate the effects of breast cancer demonstrating an ability to inhibit the processes of cell proliferation, migration, and invasion as well as EMT by suppressing the expression of PITX2 and activation of the Wnt-β-catenin pathway.
乳腺癌仍然是全球女性发病率和死亡率的首要原因之一。在本研究中,通过 Wnt-β-catenin 信号通路研究了 miR-590-5p 和同源异型盒转录因子 2(PITX2)对人乳腺癌细胞增殖、侵袭、迁移和上皮间质转化(EMT)的影响。从 KEGG 数据库中获得乳腺癌相关基因和相关信号通路。预测 PITX2 调节 microRNA。为了确定 miR-590-5p 影响乳腺癌进展的贡献作用,探讨了 miR-590-5p 与 PITX2 之间的相互作用;通过过表达或沉默 miR-590-5p 检测了其对裸鼠增殖、侵袭和迁移能力以及肿瘤生长和转移的影响。发现 PITX2 与乳腺癌具有相关性,选择 miR-590-5p 进行进一步分析。与相邻正常组织相比,乳腺癌组织中 PITX2、Wnt-1、β-catenin、N-cadherin 和波形蛋白表达水平较高,而 miR-590-5p 和 E-cadherin 表达水平较低。过表达 miR-590-5p 或 si-PITX2 后,E-cadherin 的表达明显增加,Wnt-1、β-catenin、N-cadherin 和波形蛋白的表达减少,细胞增殖、侵袭、迁移和转移以及 EMT 受到抑制。本研究表明,过表达 miR-590-5p 的转染可以减轻乳腺癌的影响,通过抑制 PITX2 的表达和激活 Wnt-β-catenin 通路,抑制细胞增殖、迁移和侵袭以及 EMT。