The Center for Heart Development, State Key Laboratory of Development Biology of Freshwater Fish, Key Laboratory of MOE for Development Biology and Protein Chemistry, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
The Second Department of Thoracic Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xianga School of Medicine, Central South University, Changsha, Hunan 410013, China.
Curr Mol Med. 2018;18(2):109-115. doi: 10.2174/1566524018666180705113642.
Previously, we showed that the Zinc finger-containing transcription factor ZNF424 inhibits p21 transcription, which has been widely associated with various cancers. However, because the roles of ZNF424 in tumorigenesis have not been characterized, we correlated ZNF424 expression with tumorigenesis in lung cancer.
The present immunohistochemical analyses show significantly lower ZNF424 expression levels in 43 of 60 lung cancer tissues compared with adjacent tissues. Moreover, flow cytometry assays indicated that overexpression of ZNF424 induces apoptosis in A549 human lung carcinoma cells, and overexpression of ZNF424 significantly increases numbers of G1 phase cells and decreases numbers of S phase cells, suggesting that ZNF424 inhibits proliferation. Western Blot analyses show that overexpression of ZNF424 decreases protein expression levels of the mitogen-activated protein kinase (MAPK) signaling proteins P-P38 and P-ERK in A549 cells.
These are the first data to associate ZNF424 with tumorigenesis and demonstrate an inhibitory role in lung cancer, indicating the potential of ZNF424 expression as a diagnostic marker of lung tumorigenesis.
此前,我们发现含锌指转录因子 ZNF424 抑制与多种癌症广泛相关的 p21 转录。然而,由于 ZNF424 在肿瘤发生中的作用尚未被阐明,我们将 ZNF424 的表达与肺癌的肿瘤发生相关联。
本免疫组织化学分析显示,与相邻组织相比,在 60 例肺癌组织中的 43 例中 ZNF424 的表达水平明显降低。此外,流式细胞术检测表明,ZNF424 的过表达可诱导 A549 人肺癌细胞凋亡,并且 ZNF424 的过表达显著增加 G1 期细胞的数量并减少 S 期细胞的数量,表明 ZNF424 抑制增殖。Western Blot 分析表明,ZNF424 的过表达降低 A549 细胞中丝裂原活化蛋白激酶(MAPK)信号蛋白 P-P38 和 P-ERK 的蛋白表达水平。
这些是首次将 ZNF424 与肿瘤发生相关联,并证明其在肺癌中具有抑制作用的研究数据,表明 ZNF424 表达作为肺癌肿瘤发生的诊断标志物的潜力。