miR-205 promotes epithelial-mesenchymal transition by targeting AKT signaling in endometrial cancer cells
miR-205 promotes epithelial-mesenchymal transition by targeting AKT signaling in endometrial cancer cells
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DOI：
10.1111/jog.12756
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发表时间：
2015-10-01
影响因子：
1.6
通讯作者：
Liang, Ruojia
中科院分区：
文献类型：
--
作者：
Jin, Chenyu;Liang, Ruojia
AimAKT信号调节多种生物学过程，并在多种肿瘤中表达。MIR-205在肿瘤的发生和发展中发挥着复杂的作用，根据肿瘤类型的不同，既可以作为肿瘤抑制因子，也可以作为癌基因。本文阐述了miR-205通过激活AKT信号通路调控子宫内膜癌细胞HEC-50B和HEC-1-A上皮-间充质转化的分子机制。材料与方法用WST-1比色法检测miR-205模拟物对HEC-50B细胞增殖的影响。通过BD跨井迁移和基质侵袭实验评价BD的迁移和侵袭能力。结果发现miR-205可促进HEC-50B细胞的增殖。MiR-205可促进HEC-50B细胞和HEC-1-A细胞的迁移和侵袭。当HEC-50B细胞和HEC-1-A细胞经抗miR-205抑制剂处理后，其迁移和侵袭能力较阴性对照细胞减少。MiR-205的过表达通过激活AKT，下调糖原合成酶K3的表达，抑制E-钙粘蛋白的表达，促进Snail的表达。然而，抗miR-205抑制剂处理HEC-50B细胞和HEC-1-A细胞后，通过抑制AKT的表达，上调E-钙粘蛋白的表达，降低Snail蛋白的表达。结论miR-205通过靶向AKT通路，在子宫内膜癌的侵袭转移中发挥重要作用。我们的数据强调miR-205是治疗子宫内膜癌的潜在分子靶点。
AimAKT signaling regulates multiple biological processes and expresses in various cancers. miR-205 plays complex roles in tumorigenesis and tumor progression by acting either as a tumor suppressor or an oncogene depending on the tumor type. Here we describe the molecular mechanism of miR-205 regulating epithelial-mesenchymal transition by activation of AKT signaling in endometrial cancer cells HEC-50B and HEC-1-A.Material and MethodsThe proliferation of HEC-50B cells transfected with miR-205 mimic was assessed by WST-1 assay. The migration and invasion were evaluated by BD transwell migration and matrigel invasion assays. The EMT markers were detected by Western blot.ResultsWe found that miR-205 increased the proliferation in HEC-50B cells. The migration and invasion of HEC-50B cells and HEC-1-A cells were enhanced by miR-205. When HEC-50B cells and HEC-1-A cells were treated with anti-miR-205 inhibitor, the migration and invasion were decreased as compared with the negative control. The overexpression of miR-205 inhibited E-cadherin expression and promoted Snail expression by activation of AKT and downregulation of glycogen synthase kinase 3. However, after the HEC-50B cells and HEC-1-A cells were treated with anti-miR-205 inhibitor, E-cadherin expression was increased and Snail protein level was decreased by inhibition of AKT expression.ConclusionOur data strongly suggest that miR-205 plays an important role in endometrial cancer migration and invasion by targeting the AKT pathway. Our data highlight miR-205 as a potential molecular target for endometrial cancer treatment.