Wang Xu, Sun Di, Tai Jiandong, Chen Si, Hong Sen, Wang Lei
Department of Colorectal and Anal Surgery, The First Hospital of Jilin University, Changchun, Jilin 130000, China.
Mol Ther Oncolytics. 2019 Jan 25;12:204-213. doi: 10.1016/j.omto.2019.01.002. eCollection 2019 Mar 29.
Aberrant expression of zinc-finger proteins has been extensively reported to contribute to malignant progression in a variety of cancers. However, clinical significance and biological roles of ZNF280A in the field of cancer are poorly known. In this study, the expression of ZNF280A was detected in clinical colorectal cancer (CRC) tissues. Functional experiments and animal experiment were performed to measure the effect of ZNF280A on the proliferation and tumorigenesis in CRC cells. Western blot and luciferase assays were used to identify the underlying pathway mediating the biological roles of ZNF280A in CRC. Here we report that ZNF280A was upregulated in CRC tissues and cells and a high expression of ZNF280A correlated with tumor, lymph node, and metastasis (TNM) classifications, clinical stage, and predicted poor prognosis and disease progression in CRC patients. Moreover, silencing ZNF280A repressed proliferation and induced G0 and/or G1 arrest , and it inhibited tumorigenesis of CRC cells . Our results further demonstrate that silencing ZNF280A inhibited the proliferation of CRC cells by activating Hippo signaling. Therefore, our results uncover a novel mechanistic understanding of ZNF280A-mediated tumor progression in CRC, and meanwhile they provide a novel prognostic factor in CRC patients and a potential therapeutic target for the treatment of CRC.
锌指蛋白的异常表达已被广泛报道与多种癌症的恶性进展有关。然而，ZNF280A在癌症领域的临床意义和生物学作用却鲜为人知。在本研究中，检测了临床结直肠癌（CRC）组织中ZNF280A的表达。进行了功能实验和动物实验，以测定ZNF280A对CRC细胞增殖和肿瘤发生的影响。采用蛋白质免疫印迹法和荧光素酶测定法来确定介导ZNF280A在CRC中生物学作用的潜在途径。在此我们报告，ZNF280A在CRC组织和细胞中上调，ZNF280A的高表达与肿瘤、淋巴结和转移（TNM）分类、临床分期相关，且预示CRC患者预后不良和疾病进展。此外，沉默ZNF280A可抑制增殖并诱导G0和/或G1期阻滞，还能抑制CRC细胞的肿瘤发生。我们的结果进一步证明，沉默ZNF280A通过激活Hippo信号通路抑制CRC细胞的增殖。因此，我们的结果揭示了对ZNF280A介导的CRC肿瘤进展的新机制理解，同时为CRC患者提供了一种新的预后因素以及治疗CRC的潜在治疗靶点。
