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Knockdown of astrocyte elevated gene-1 (AEG-1) in cervical cancer cells decreases their invasiveness epithelial to mesenchymal transition and chemoresistance

机译:敲低宫颈癌细胞中星形胶质细胞升高基因1(AEG-1)会降低其侵袭性上皮向间质转化以及化学抗药性

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摘要

During cancer development, epithelial–mesenchymal transition (EMT) facilitates tumor dissemination and metastatic spread, which is characterized by morphologic changes from epithelial cells to fibroblast-like cells, disassembly of intercellular junction, and increased cell motility. Overexpression of astrocyte elevated gene-1(AEG-1) in various cancer cell lines and cancers has been found to be associated with aggressive tumor behavior. We found that AEG-1 expression was elevated in low differentiation cervical cancer specimens from patients. However, little is known about the AEG-1’s precise role in invasion and metastasis. Here we demonstrate that downregulation of AEG-1 by RNAi significantly decreased the invasion and migration of cervical cancer cells, suggesting that AEG-1 overexpression may enhance cancer cell motility by inducing EMT. Downregulation of AEG-1 also led to reduced expression of mesenchymal marker vimentin and the transcription factor Snail but upregulation of epithelial marker E-cadherin in HeLa cells. In addition, knockdown of AEG-1 decreased colony forming units and increased sensitivity to cancer drugs in vitro. Taken together, our results suggest that knockdown of AEG-1 could decrease EMT and chemoresistance in cervical cancer cells and attenuate their aggressive behavior.
机译:在癌症发展过程中,上皮-间质转化(EMT)促进了肿瘤的扩散和转移扩散,其特征是从上皮细胞到成纤维细胞样细胞的形态变化,细胞间连接的拆卸和细胞运动性的增强。星形胶质细胞升高基因-1(AEG-1)在各种癌细胞系和癌症中的过表达已被发现与侵略性肿瘤行为有关。我们发现在来自患者的低分化宫颈癌标本中AEG-1表达升高。但是,人们对AEG-1在侵袭和转移中的确切作用知之甚少。在这里,我们证明RNAi对AEG-1的下调显着降低了宫颈癌细胞的侵袭和迁移,这表明AEG-1的过表达可能通过诱导EMT增强癌细胞的运动性。 AEG-1的下调还导致间充质标记波形蛋白和转录因子Snail的表达减少,但上皮标记E-钙粘蛋白在HeLa细胞中的表达上调。此外,敲除AEG-1会降低菌落形成单位,并增加体外对癌症药物的敏感性。综上所述,我们的结果表明,敲低AEG-1可以降低子宫颈癌细胞的EMT和化学抗性,并减弱其侵袭行为。

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