Chen Xin, Zheng Qi, Li Weidong, Lu Yuan, Ni Yiming, Ma Liang, Fu Yufei
Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang 310003, P. R. China,
Zhejiang Key Laboratory of Gastro-Intestinal Pathophysiology, Zhejiang Hospital of Traditional Chinese Medicine, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P. R. China,
Onco Targets Ther. 2018 Sep 11;11:5733-5741. doi: 10.2147/OTT.S176533. eCollection 2018.
Angiogenesis is the main cause of lung adenocarcinoma (LAC) poor prognosis. This study aimed to investigate the effect of sex-determining region Y-box protein 5 (SOX5) expression on angiogenesis of LAC and explore its possible mechanism.
The effect on angiogenesis was tested by tube formation assays using human umbilical vein endothelial cells cocultured with A549 cells. Lentivirus shRNA of SOX5 and lentivirus of SOX5 overexpression system were used to establish LAC cell lines, which expressed SOX5 of different levels. SOX5 downstream signaling targets were analyzed by real-time qPCR and Western blot. We collected 90 LAC cases and the tissues were examined by immunohistochemistry for SOX5 and vascular endothelial growth factor (VEGF).
We found that SOX5 overexpression in A549 cells significantly promoted tube formation capacity of the cocultured human umbilical vein endothelial cells. SOX5 increased VEGF expression and signal transducer activator of transcription 3 phosphorylation; however, SOX5 had no effect on extracellular signal-regulated kinase and protein kinase B pathway. Furthermore, the expression of SOX5 and VEGF had a significantly positive correlation (=0.399, =0.001) according to the tissue microarray data.
These findings suggest that SOX5 induces angiogenesis by activating signal transducer activator of transcription 3/VEGF signaling and confer its candidacy as a potential therapeutic target in LAC.
血管生成是肺腺癌（LAC）预后不良的主要原因。本研究旨在探讨性别决定区Y盒蛋白5（SOX5）表达对LAC血管生成的影响，并探索其可能机制。
采用人脐静脉内皮细胞与A549细胞共培养的管腔形成实验检测血管生成情况。利用SOX5慢病毒短发夹RNA（shRNA）和SOX5过表达系统慢病毒建立不同SOX5表达水平的LAC细胞系。通过实时定量聚合酶链反应（qPCR）和蛋白质免疫印迹法分析SOX5下游信号靶点。收集90例LAC病例，采用免疫组织化学法检测组织中SOX5和血管内皮生长因子（VEGF）。
我们发现A549细胞中SOX5过表达显著促进共培养的人脐静脉内皮细胞的管腔形成能力。SOX5增加VEGF表达及信号转导子和转录激活子3（STAT3）磷酸化；然而，SOX5对细胞外信号调节激酶和蛋白激酶B通路无影响。此外，根据组织芯片数据，SOX5与VEGF表达呈显著正相关（r = 0.399，P = 0.001）。
这些发现表明，SOX5通过激活STAT3/VEGF信号诱导血管生成，使其有潜力成为LAC的治疗靶点。
