Wang J, Huang H H, Liu F B
Department of Thoracic Surgery, The First Peoples Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China.
J Biol Regul Homeost Agents. 2016 Jul-Sep;30(3):683-691.
Zinc finger (ZNF) proteins, a diverse family of proteins, have multiple biological functions in cancer. Increased expression of ZNF185 has been involved in the regulation of tumor growth and metastasis. However, the function and underlying mechanisms of ZNF185 in the tumorigenesis of lung adenocarcinoma (LAC) remain unclear. The protein expression of ZNF185 was examined in human LAC tissues by immunohistochemical assay. After lentiviral vector-mediated ZNF185 overexpression was infected into the LAC cell lines (A549 and LETPα-2), cell growth and invasive potential were respectively evaluated by MTT and Transwell assays. We found that the protein expression of ZNF185 was significantly downregulated in LAC tissues compared with the adjacent non-cancerous tissues (ANCT) (37.10% vs 58.06%, P=0.015), and was negatively correlated with the lymph node metastasis of the LAC patients (P=0.005). Furthermore, overexpression of ZNF185 reduced cell proliferation and invasion in LAC cells, followed by the downregulation of p-AKT, p-GSK3β, VEGF and MMP-9 expression. Taken together, our findings indicate that the decreased expression of ZNF185 is linked to the tumor metastasis in human LAC patients, and ZNF185 overexpression inhibits the growth and invasion of LAC cells through inhibition of the AKT/GSK3β signaling, suggesting that ZNF185 may represent a potential therapeutic target for the treatment of LAC.
锌指（ZNF）蛋白是一类多样的蛋白质家族，在癌症中具有多种生物学功能。ZNF185表达的增加与肿瘤生长和转移的调控有关。然而，ZNF185在肺腺癌（LAC）肿瘤发生中的功能及潜在机制仍不清楚。通过免疫组织化学分析检测了人LAC组织中ZNF185的蛋白表达。在将慢病毒载体介导的ZNF185过表达感染到LAC细胞系（A549和LETPα-2）后，分别通过MTT和Transwell实验评估细胞生长和侵袭潜能。我们发现，与相邻非癌组织（ANCT）相比，LAC组织中ZNF185的蛋白表达显著下调（37.10%对58.06%，P = 0.015），并且与LAC患者的淋巴结转移呈负相关（P = 0.005）。此外，ZNF185的过表达降低了LAC细胞的增殖和侵袭，随后p-AKT、p-GSK3β、VEGF和MMP-9的表达下调。综上所述，我们的研究结果表明，ZNF185表达降低与人类LAC患者的肿瘤转移有关，ZNF185过表达通过抑制AKT/GSK3β信号通路抑制LAC细胞的生长和侵袭，提示ZNF185可能是治疗LAC的潜在治疗靶点。
