MicroRNA-144-3p suppressed TGF-β1-induced lung cancer cell invasion and adhesion by regulating the Src-Akt-Erk pathway
MicroRNA-144-3p suppressed TGF-β1-induced lung cancer cell invasion and adhesion by regulating the Src-Akt-Erk pathway
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DOI：
10.1002/cbin.11158
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发表时间：
2020-01-01
影响因子：
3.9
通讯作者：
Yang, Jun
中科院分区：
文献类型：
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作者：
Jiang, Wensheng;Xu, Zhiying;Yang, Jun
肺癌仍然是全球癌症相关死亡的主要原因。MicroRNA-144-3p的抗癌作用已在多种癌症类型中得到报道。本研究旨在探讨miR-144-3p抑制肺癌的机制。比较miR-144-3p和类固醇受体辅活化子(Src)在不同肺癌细胞系和支气管上皮细胞(16HBE)中的表达。将miR-144-3p Mimic和siSrc分别导入A549细胞。在转化生长因子-β1(TGF-β1)的条件下。通过Transwell和细胞黏附实验分析小干扰基因和转化生长因子-β1处理对细胞侵袭和黏附能力的影响。将miR-144-3p抑制剂与siSrc共转染A549细胞，检测细胞侵袭和黏附能力的变化。Western印迹法检测细胞外调节蛋白激酶(Src-Akt-Erk)通路的激活。在肺癌细胞系中普遍检测到miR-144-3p的下调和Src的上调，在A549细胞中是最显著的基因。在有或无转化生长因子-β1作用的情况下，miR-144-3p过表达和Src抑制均能明显抑制A549细胞的侵袭和黏附能力。抑制src可阻断miR-144-3p抑制剂和转化生长因子-β1对细胞侵袭和黏附的促进作用。此外，我们还发现miR-144-3p可以负向调节Akt和Erk的磷酸化水平。提示Src在转化生长因子-β1诱导的肺癌细胞侵袭和黏附机制中起重要作用，miR-144-3p可通过调节src的表达而有效抑制转化生长因子-β1诱导的肺癌细胞侵袭性。
Lung cancer remains a leading cause to cancer-related death worldwide. The anti-cancer ability of microRNA-144-3p has been reported in many cancer types. This study focused on the mechanisms underlying miR-144-3p in inhibiting lung cancer. The expression levels of miR-144-3p and steroid receptor coactivator (Src) in different lung cancer cell lines and those in bronchial epithelial cells (16HBE) were compared. miR-144-3p mimic and siSrc were transfected into A549 cells. Under the conditions of transforming growth factor-beta 1 (TGF-beta 1). Small interfering transfection or TGF-beta 1 treatment, cell invasive and adhesive abilities were analyzed by Transwell and cell adhesion assays. miR-144-3p inhibitor and siSrc were co-transfected into A549 cells and the changes in cell invasion and adhesion were detected. The activation of Src-protein kinase B-extracellular-regulated protein kinases (Src-Akt-Erk) pathway was determined using Western blot. The downregulated miR-144-3p and upregulated Src were generally detected in lung cancer cell lines and were the most significant genes in A549 cells. Both miR-144-3p overexpression and Src inhibition could obviously inhibit the invasion and adhesion abilities of A549 cells in the presence or absence of the effects of TGF-beta 1. The inhibition of Src could block the promotive effects of miR-144-3p inhibitor and TGF-beta 1 on cell invasion and adhesion. Furthermore, we found that miR-144-3p could negatively regulate the phosphorylation levels of Akt and Erk. Our data indicated the essential role of Src in the mechanisms underlying TGF-beta 1-induced cell invasion and adhesion of lung cancer, and that miR-144-3p could effectively suppress TGF-beta 1-induced aggressive lung cancer cells by regulating Src expression.