The NF-κB-modulated miR-19a-3p enhances malignancy of human ovarian cancer cells through inhibition of IGFBP-3 expression
The NF-κB-modulated miR-19a-3p enhances malignancy of human ovarian cancer cells through inhibition of IGFBP-3 expression
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NF-κB调节的miR-19a-3p通过抑制IGFBP-3表达增强人卵巢癌细胞的恶性程度
DOI：
10.1002/mc.23113
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发表时间：
2019-09-12
影响因子：
4.6
通讯作者：
Sun, Jianmin
中科院分区：
文献类型：
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作者：
Bai, Ru;Cui, Zhenhua;Sun, Jianmin
卵巢癌是妇科恶性肿瘤中最具致命性的一种，直到晚期才出现症状，迫切需要新的诊断和治疗策略。在本研究中，我们发现miR-19a-3p在卵巢癌组织中的表达高于癌旁正常组织。通过染色质免疫沉淀（ChIP）和电泳迁移迁移试验（EMSA）分析，我们发现核因子- κ B （nf - κ B）与miR-19a-3p的启动子结合，导致卵巢癌细胞中miR-19a-3p的表达降低。进一步研究表明，miR-19a-3p抑制胰岛素样生长因子结合蛋白-3 （IGFBP-3）的表达，从而促进卵巢癌细胞在体外的生长和迁移以及体内的肿瘤生长。这些结果表明，miR-19a-3p通过抑制IGFBP-3的表达而促进卵巢癌的癌变，而IGFBP-3可被NF-kappa B抑制，提示NF-kappa B/miR-19a-3p/IGFBP-3通路参与卵巢癌的癌变，扩大了我们对卵巢癌的认识，并可能有助于卵巢癌新诊断和治疗的开发。
Ovarian cancer is the most lethal gynecologic malignancy due to the lack of symptoms until advanced stages, and new diagnosis and treatment strategy is in urgent need. In this study, we found higher expression of miR-19a-3p in ovarian cancer tissues compared with that in the adjacent normal tissues. By chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA) analysis, we showed that nuclear factor-kappaB (NF-kappa B) binds to the promoter of miR-19a-3p, leading to reduced expression in ovarian cancer cells. Further study indicated that miR-19a-3p inhibits the expression of insulin-like growth factor binding protein-3 (IGFBP-3), resulting in enhanced growth and migration of ovarian cancer cells in vitro and tumor growth in vivo. These results showed that miR-19a-3p enhances the oncogenesis of ovarian cancer through inhibition of IGFBP-3 expression, and which can be inhibited by NF-kappa B, suggesting an NF-kappa B/miR-19a-3p/IGFBP-3 pathway in the oncogenesis of ovarian cancer, which expands our understanding of ovarian cancer and they may contribute to the development of new diagnosis and treatment of ovarian cancer.