MicroRNA-424 inhibits cell migration, invasion, and epithelial mesenchymal transition by downregulating doublecortin-like kinase 1 in ovarian clear cell carcinoma.
MicroRNA-424 inhibits cell migration, invasion, and epithelial mesenchymal transition by downregulating doublecortin-like kinase 1 in ovarian clear cell carcinoma.
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MicroRNA-424 通过下调卵巢透明细胞癌中的双皮质素样激酶 1 来抑制细胞迁移、侵袭和上皮间质转化。
DOI：
10.1016/j.biocel.2017.01.020
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发表时间：
2017-04
影响因子：
4
通讯作者：
武欣
中科院分区：
文献类型：
--
作者：
武欣
双重皮质醇样激酶1(DCLK1)在许多肿瘤中高表达，是一种肿瘤干细胞标记物。在这里，我们研究了DCLK1和microRNA-424(miR-424)在卵巢透明细胞癌(OCCC)中的作用。卵巢透明细胞癌是卵巢上皮癌的一种组织病理学亚型，与预后不良和化疗耐药有关。对30例OCCC患者标本的分析表明，与癌旁组织相比，肿瘤组织中DCLK1表达上调，miR-424表达下调。DCLK1过表达促进OCCC细胞的增殖、迁移和侵袭，而DCLK1基因敲除降低了细胞的存活率和侵袭力，并在体内诱导生长。双荧光素酶分析显示miR-424直接靶向DCLK1并下调其表达。用miR-424基因转染ES-2细胞可模拟DCLK1的下调，并抑制DCLK1过表达上调基质金属蛋白酶-9和促进上皮-间充质转化(EMT)的作用。综上所述，这些数据表明miR-424有能力通过下调DCLK1来抑制OCCC的细胞侵袭和EMT，为该疾病的治疗提供了潜在的治疗靶点和策略。
Doublecortin-like kinase 1 (DCLK1) is overexpressed in many cancers and acts as a tumor stem cell marker. Here, we investigated the role of DCLK1 and microRNA-424 (miR-424) in ovarian clear cell carcinoma (OCCC), a histopathologically distinct subtype of epithelial ovarian cancer associated with poor prognosis and chemotherapy resistance. Analysis of samples from 30 OCCC patients showed that DCLK1 was upregulated and miR-424 was downregulated in tumors compared with adjacent non-tumor tissues. DCLK1 overexpression promoted OCCC cell proliferation, migration, and invasion, whereas DCLK1 knockdown reduced cell viability and invasion and induced growth arrestin vitroandin vivo. Dual-luciferase reporter assays revealed that miR-424 directly targets DCLK1 and downregulates its expression. Transfection of ES-2 cells with miR-424 mimics downregulated DCLK1 and suppressed the effects of DCLK1 overexpression on upregulating matrix metalloprotease-9 and promoting epithelial-mesenchymal transition (EMT). Taken together, these data demonstrate that miR-424 has the capacity to suppress cell invasion and EMT in OCCC by downregulating DCLK1, suggesting potential therapeutic targets and strategies for the treatment of this disease.
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