关键词: Cdc42, Cell division cycle 42 DMEM, Dulbecco's Modified Eagle's Medium EMT EMT, Epithelial-to-Mesenchymal Transition ERK, Extracellular signal-related kinase FBS, Fetal Bovine Serum LUAD, Lung adenocarcinoma Lung adenocarcinoma MEK, Mitogen-activated protein kinase kinase NSCLC, Non-Small-Cell Lung Cancer RhoQ SDS, Sodium Dodecyl Sulfate TGF-β TGF-β, Transforming Growth Factor-beta TRITC, tetramethylrhodamine-isothiocyanate qPCR, Quantitative Polymerase Chain Reaction rRNA, Ribosomal ribonucleic acid siRNA, Small Interfering RNA Cdc42, Cell division cycle 42 DMEM, Dulbecco's Modified Eagle's Medium EMT EMT, Epithelial-to-Mesenchymal Transition ERK, Extracellular signal-related kinase FBS, Fetal Bovine Serum LUAD, Lung adenocarcinoma Lung adenocarcinoma MEK, Mitogen-activated protein kinase kinase NSCLC, Non-Small-Cell Lung Cancer RhoQ SDS, Sodium Dodecyl Sulfate TGF-β TGF-β, Transforming Growth Factor-beta TRITC, tetramethylrhodamine-isothiocyanate qPCR, Quantitative Polymerase Chain Reaction rRNA, Ribosomal ribonucleic acid siRNA, Small Interfering RNA

来  源:   DOI:10.1016/j.bbrep.2022.101346   PDF(Pubmed)

Abstract:
Lung cancer is the leading cause of cancer-related deaths worldwide, and the most common subtype of lung cancer is adenocarcinoma. RhoQ is a Rho family GTPase with primary sequence and structural similarities to Cdc42 and RhoJ. RhoQ is involved in neurite outgrowth via membrane trafficking and is essential for insulin-stimulated glucose uptake in mature adipocytes. However, the function of RhoQ in lung adenocarcinoma (LUAD) remains unclear. In this study, RhoQ siRNAs were introduced into A549 and PC-9 cells. Expression level of EMT-related genes and invasion ability were investigated using Western blot and transwell assay. To examine the relationship between RhoQ expression and prognosis of LUAD, Kaplan-Meier plotter was used. We discovered that suppressing RhoQ expression promoted TGF-β-mediated EMT and invasion in LUAD cell lines. Furthermore, RhoQ knockdown increased Smad3 phosphorylation and Snail expression, indicating that RhoQ was involved in TGF/Smad signaling during the EMT process. Moreover, Kaplan-Meier plotter analysis revealed that low RhoQ levels were associated with poor overall survival in patients with LUAD. In conclusion, these findings shed light on RhoQ\'s role as a negative regulator of TGF-β-mediated EMT in LUAD.
摘要:
肺癌是全球癌症相关死亡的主要原因,最常见的肺癌亚型是腺癌。RhoQ是Rho家族GTP酶,具有与Cdc42和RhoJ的一级序列和结构相似性。RhoQ通过膜运输参与神经突生长,并且对于成熟脂肪细胞中胰岛素刺激的葡萄糖摄取至关重要。然而,RhoQ在肺腺癌(LUAD)中的作用尚不清楚.在这项研究中,将RhoQsiRNA引入A549和PC-9细胞中。采用Westernblot和transwell法检测EMT相关基因的表达水平和侵袭能力。探讨RhoQ表达与LUAD预后的关系,使用Kaplan-Meier绘图仪。我们发现抑制RhoQ表达可促进TGF-β介导的EMT和LUAD细胞系的侵袭。此外,RhoQ敲低增加Smad3磷酸化和蜗牛表达,表明RhoQ在EMT过程中参与TGF/Smad信号传导。此外,Kaplan-Meier绘图仪分析显示,低RhoQ水平与LUAD患者总体生存率低相关。总之,这些发现揭示了RhoQ在LUAD中作为TGF-β介导的EMT的负调节因子的作用。
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