Wang Lei, Hu Fengqing, Shen Saie, Xiao Haibo, Li Guoqing, Wang Mingsong, Mei Ju
Department of Cardiothoracic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092, China.
Department of Anesthesiology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092, China.
Am J Transl Res. 2017 Sep 15;9(9):4003-4014. eCollection 2017.
Sex determining region Y-box protein 12 (SOX12) plays an important role in the tumorigenesis of hepatocellular carcinoma. The involvement of SOX12 in human lung cancer is not well-understood. The aim of the current study was to explore the expression pattern and function of SOX12 in lung cancer. SOX12 expression in lung cancer tissues was elevated as assessed by analyzing The Cancer Genome Atlas (TCGA) lung cancer cohort and real-time PCR data of our own cohort. We found that SOX12 mRNA expression was up-regulated in 83.3% (75/90) of the lung cancer tissues in comparison with paired normal tissues. Moreover, high SOX12 expression predicted reduced overall survival. We also found that knockdown of SOX12 in SPC-A-1 and A549 cells impaired lung cancer cell proliferation, migration and invasion , but promoted lung cancer cell apoptosis. tumorigenesis experiments showed that inhibition of SOX12 expression significantly suppressed the growth of xenograft tumors. Finally, the mRNA and protein levels of cell growth (PCNA and Cyclin E), apoptosis (Bcl-2 and Bax), invasion (matrix metalloproteinase-9) and epithelial-mesenchymal transition (EMT; Twist1 and E-cadherin) related moderators were affected by SOX12 knockdown. Chromatin immunoprecipitation assays showed that Cyclin E and Twist1 were direct transcriptional targets of SOX12. Taken together, our study suggests that SOX12 functions as an oncogenic molecule during the development of human lung cancer.
Y染色体性别决定区框蛋白12(SOX12)在肝细胞癌的肿瘤发生过程中发挥重要作用。SOX12在人类肺癌中的作用尚未完全明确。本研究旨在探讨SOX12在肺癌中的表达模式及功能。通过分析癌症基因组图谱(TCGA)肺癌队列以及我们自己队列的实时PCR数据评估发现,肺癌组织中SOX12表达升高。我们发现,与配对的正常组织相比,83.3%(75/90)的肺癌组织中SOX12 mRNA表达上调。此外,SOX12高表达预示着总生存期缩短。我们还发现,敲低SPC-A-1和A549细胞中的SOX12会损害肺癌细胞的增殖、迁移和侵袭,但会促进肺癌细胞凋亡。肿瘤发生实验表明,抑制SOX12表达可显著抑制异种移植肿瘤的生长。最后,细胞生长(PCNA和细胞周期蛋白E)、凋亡(Bcl-2和Bax)、侵袭(基质金属蛋白酶-9)和上皮-间质转化(EMT;Twist1和E-钙黏蛋白)相关调节因子的mRNA和蛋白水平受到SOX12敲低的影响。染色质免疫沉淀试验表明,细胞周期蛋白E和Twist1是SOX12的直接转录靶点。综上所述,我们的研究表明SOX12在人类肺癌发生过程中作为一种致癌分子发挥作用。