Knockdown of long non-coding RNA linc-ITGB1 inhibits cancer stemness and epithelial-mesenchymal transition by reducing the expression of Snail in non-small cell lung cancer
Knockdown of long non-coding RNA linc-ITGB1 inhibits cancer stemness and epithelial-mesenchymal transition by reducing the expression of Snail in non-small cell lung cancer
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长链非编码RNA linc-ITGB1的敲低通过减少非小细胞肺癌中Snail的表达来抑制癌症干细胞性和上皮间质转化
DOI：
10.1111/1759-7714.12911
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发表时间：
2019-02-01
期刊：
影响因子：
2.9
通讯作者：
Guo, Fengjie
中科院分区：
文献类型：
--
作者：
Guo, Lili;Sun, Cencen;Guo, Fengjie
背景 非小细胞肺癌（NSCLC）患者死亡的主要原因是癌症转移的进展，其可归因于多种因素，例如癌症干细胞（CSC）和上皮间质转化（EMT）。长非编码RNA (lncRNA)在癌症的细胞周期、细胞增殖、免疫反应和转移的调节中发挥重要作用，但lincRNA在癌症CSC样特性中的潜在作用和机制尚未阐明。方法 对人 NSCLC 细胞系（A549 和 H1299）、高转移细胞系（L9981 和 95D）及其相应的低转移细胞系（NL9980 和 95C）进行定量实时 PCR 和 Western blot、transwell 侵袭、集落形成和伤口愈合测定。结果 Linc-ITGB1 在 CSC 球体中显着上调。 Linc-ITGB1 敲低显着抑制 CSC 形成和干性相关基因的表达，例如 Sox2、Nanog、Oct-4、c-Myc 和 CD133。 linc-ITGB1表达的缺失也抑制了细胞的体外侵袭和迁移潜力，进一步分析表明，linc-ITGB1敲除增加了上皮标记物E-cadherin的表达，并下调了间充质标记物波形蛋白和纤连蛋白的表达。 EMT 相关转录因子 Snail 介导 linc-ITGB1 在 NSCLC 中的这些作用，并且 Snail 的过表达显着逆转 linc-ITGB1 缺失的抑制作用。结论 总体而言，我们的研究表明 linc-ITGB1 通过调节 Snail 表达促进 NSCLC 细胞 EMT 和癌症干细胞性。
Background The main cause of death in patients with non-small cell lung cancer (NSCLC) is the progression of cancer metastasis, which can be attributed to multiple factors, such as cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT). Long non-coding RNAs (lncRNAs) play important roles in the regulation of the cell cycle, cell proliferation, immune responses, and metastasis in cancers, but the potential roles and mechanisms of lincRNAs in CSC-like properties of cancer have not yet been elucidated. Methods Human NSCLC cell lines (A549 and H1299), highly metastatic cell lines (L9981 and 95D), and their corresponding low-metastatic cell lines (NL9980 and 95C) were subject to quantitative real-time PCR and Western blot, transwell invasion, colony formation, and wound healing assays. Results Linc-ITGB1 was greatly upregulated in CSC spheres. Linc-ITGB1 knockdown markedly inhibited CSC formation and the expression of stemness-associated genes, such as Sox2, Nanog, Oct-4, c-Myc, and CD133. Depletion of linc-ITGB1 expression also inhibited the in vitro invasive and migratory potential of cells, and further analysis indicated that linc-ITGB1 knockdown increased the expression of the epithelial marker E-cadherin and downregulated the mesenchymal markers vimentin and fibronectin. The EMT-related transcription factor Snail mediated these effects of linc-ITGB1 in NSCLC, and overexpression of Snail significantly reversed the inhibitory effects of linc-ITGB1 depletion. Conclusion Overall, our study demonstrated that linc-ITGB1 promoted NSCLC cell EMT and cancer stemness by regulating Snail expression.