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Silencing LINC00511 inhibits cell proliferation, migration, and epithelial-mesenchymal transition via the PTEN-AKT-FOXO1 signaling pathway in lung cancer.
Biochemistry and Cell Biology ( IF 2.4 ) Pub Date : 2019-08-15 , DOI: 10.1139/bcb-2018-0364
Lianyong Jiang 1 , Xiao Xie 1 , Fangbao Ding 1, 1 , Ju Mei 1, 1 , Rui Bi 1, 1
Affiliation  

Lung cancer is the most common cause of cancer-related death worldwide. Long noncoding RNAs (lncRNAs) are longer than 200 nt transcripts and are not translated into proteins. Increasing evidence has shown that lncRNAs are associated with several biological processes in cancer. However, the roles of LINC00511 in lung cancer progression remain unknown. In the present study, we confirmed that LINC00511 knockdown significantly inhibited cell proliferation and migration in A549, SPCA1, and H460 cells. Western blot results showed that silencing LINC00511 inhibited epithelial-mesenchymal transition (EMT), which resulted in decreased expression levels of ZEB2, N-cadherin, and vimentin and increased expression levels of E-cadherin. Additionally, silencing LINC00511 significantly upregulated PTEN mRNA and protein expression, increased FOXO1, and inactivated AKT. Furthermore, we found that PTEN knockdown reversed the inhibition of cell migration and proliferation induced by LINC00511 siRNA, markedly reduced p-FOXO1 expression, and promoted p-AKT expression and EMT in A549 and H460 cells. Therefore, these findings revealed that LINC00511 functions as an oncogene through the PTEN-AKT-FOXO1 signaling pathway in lung cancer, providing a potential target of metastasis in lung cancer.

中文翻译:

沉默 LINC00511 通过 PTEN-AKT-FOXO1 信号通路抑制肺癌细胞增殖、迁移和上皮-间质转化。

肺癌是全世界癌症相关死亡的最常见原因。长链非编码 RNA (lncRNA) 长度超过 200 nt 的转录物,不会被翻译成蛋白质。越来越多的证据表明,lncRNA 与癌症中的几个生物学过程相关。然而,LINC00511 在肺癌进展中的作用仍然未知。在本研究中,我们证实 LINC00511 敲低显着抑制 A549、SPCA1 和 H460 细胞的细胞增殖和迁移。蛋白质印迹结果显示,沉默 LINC00511 会抑制上皮-间质转化 (EMT),从而导致 ZEB2、N-cadherin 和 vimentin 的表达水平降低,而 E-cadherin 的表达水平升高。此外,沉默 LINC00511 可显着上调 PTEN mRNA 和蛋白质表达,增加 FOXO1,并灭活 AKT。此外,我们发现 PTEN 敲低逆转了 LINC00511 siRNA 诱导的细胞迁移和增殖抑制,显着降低 p-FOXO1 表达,并促进 A549 和 H460 细胞中的 p-AKT 表达和 EMT。因此,这些发现揭示了 LINC00511 通过 PTEN-AKT-FOXO1 信号通路在肺癌中发挥致癌基因的作用,为肺癌转移提供了潜在靶点。
更新日期:2019-11-01
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