Interaction of hnRNP K with MAP 1B-LC1 promotes TGF-β1-mediated epithelial to mesenchymal transition in lung cancer cells
Interaction of hnRNP K with MAP 1B-LC1 promotes TGF-β1-mediated epithelial to mesenchymal transition in lung cancer cells
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hnRNP K 与 MAP 1B-LC1 的相互作用促进肺癌细胞中 TGF-β 1 介导的上皮间质转化
DOI：
10.1186/s12885-019-6119-x
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发表时间：
2019-09-06
期刊：
影响因子：
3.8
通讯作者：
Chen, Miaojuan
中科院分区：
文献类型：
--
作者：
Li, Liping;Yan, Songxin;Chen, Miaojuan
背景异质核糖核蛋白（hnRNP）参与转移相关网络。我们之前的研究表明，hnRNP K 与 A549 细胞的上皮间质转化 (EMT) 相关。然而，hnRNP K参与TGF-β1诱导EMT的确切分子机制仍不清楚。本研究旨在探讨hnRNP K与微管相关蛋白1B轻链（MAP 1B-LC1）相互作用在TGF-β1诱导的EMT中的功能和机制。方法采用免疫组织化学法检测非小细胞肺癌（NSCLC）中hnRNP K的表达。 GST-pull down 和免疫荧光证明 MAP 1B-LC1 和 hnRNP K 之间的关联。免疫荧光、transwell 实验和蛋白质印迹用于研究 MAP 1B-LC1 与 hnRNP K 在 TGF-β 1 诱导的 A549 细胞 EMT 过程中相互作用的功能和机制。结果 hnRNP K 在 NSCLC 中高表达，且 hnRNP K 表达较高的 NSCLC 更常被评为预后较差的高级别肿瘤。 MAP 1B-LC1 被鉴定并验证为与 hnRNP K 相互作用的蛋白质之一。 MAP 1B-LC1 的敲除可抑制 E-钙粘蛋白下调、波形蛋白上调和肌动蛋白丝重塑，减少 A549 细胞中 TGF-β 1 诱导的 EMT 期间的细胞迁移和侵袭。 hnRNP K 通过与 MAP 1B-LC1 相互作用增加微管稳定性，并在 EMT 过程中与乙酰化微管蛋白相关。结论 hnRNP K通过与MAP 1B-LC1相互作用，促进TGF-β1诱导的肺癌细胞EMT过程。 MAP 1B/LC1 与 hnRNP K 的相互作用可能会提高我们对 TGF-β 1 诱导肺癌 EMT 机制的理解。
Backgrounds Heterogeneous ribonucleoproteins (hnRNPs) are involved in the metastasis-related network. Our previous study demonstrated that hnRNP K is associated with epithelial-to-mesenchymal transition (EMT) in A549 cells. However, the precise molecular mechanism of hnRNP K involved in TGF-beta 1-induced EMT remains unclear. This study aimed to investigate the function and mechanism of hnRNP K interacted with microtubule-associated protein 1B light chain (MAP 1B-LC1) in TGF-beta 1-induced EMT. Methods Immunohistochemistry was used to detect the expression of hnRNP K in non-small-cell lung cancer (NSCLC). GST-pull down and immunofluorescence were performed to demonstrate the association between MAP 1B-LC1 and hnRNP K. Immunofluorescence, transwell assay and western blot was used to study the function and mechanism of the interaction of MAP 1B-LC1 with hnRNP K during TGF-beta 1-induced EMT in A549 cells. Results hnRNP K were highly expressed in NSCLC, and NSCLC with higher expression of hnRNP K were more frequently rated as high-grade tumors with poor outcome. MAP 1B-LC1 was identified and validated as one of the proteins interacting with hnRNP K. Knockdown of MAP 1B-LC1 repressed E-cadherin downregulation, vimentin upregulation and actin filament remodeling, decreased cell migration and invasion during TGF-beta 1-induced EMT in A549 cells. hnRNP K increased microtubule stability via interacting with MAP 1B-LC1 and was associated with acetylated -tubulin during EMT. Conclusion hnRNP K can promote the EMT process of lung cancer cells induced by TGF-beta 1 through interacting with MAP 1B-LC1. The interaction of MAP 1B/LC1 with hnRNP K may improve our understanding on the mechanism of TGF-beta 1-induced EMT in lung cancer.