Song Xiaoling, Zhu Minghui, Zhang Fahong, Zhang Fei, Zhang Yijian, Hu Yunping, Jiang Lin, Hao Yajuan, Chen Shili, Zhu Qin, Huang Wen, Lu Jianhua, Gu Jun, Gong Wei, Li Maolan, Liu Yingbin
Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, China.
Cell Physiol Biochem. 2018;48(1):274-284. doi: 10.1159/000491727. Epub 2018 Jul 13.
BACKGROUND/AIMS: The role of ZFX in tumourigenesis is unclear. We aimed to study ZFX expression, regulation, and function and the clinical implications of this protein in human pancreatic cancer (PCa).
One hundred and twenty patients with histologically confirmed PCa who underwent surgery were recruited for this study. Tumour samples and PCa cell lines were used to examine ZFX. Various cell functions related to tumourigenesis were assessed. In vivo mouse tumour xenografts were used to confirm the in vitro results.
Patients with ZFX-positive tumours had worse overall survival than patients with ZFX-negative tumours. The depletion of ZFX using lentiviral shRNAs significantly inhibited cell proliferation by inducing cell cycle arrest in G0/G1 phase and resulted in increased cell apoptosis and invasive repression. In vivo studies confirmed that ZFX promoted tumour growth. Mechanistically, MAPK pathway activation was involved in the oncogenic functions of ZFX.
ZFX acts as a putative oncogene in PCa and could be a novel therapeutic target for this disease.
背景/目的：ZFX在肿瘤发生中的作用尚不清楚。我们旨在研究ZFX在人胰腺癌（PCa）中的表达、调控、功能及其临床意义。
本研究招募了120例经组织学确诊并接受手术的PCa患者。使用肿瘤样本和PCa细胞系检测ZFX。评估了与肿瘤发生相关的各种细胞功能。采用体内小鼠肿瘤异种移植模型来证实体外实验结果。
ZFX阳性肿瘤患者的总生存期比ZFX阴性肿瘤患者更差。使用慢病毒短发夹RNA（shRNAs）敲低ZFX可通过诱导细胞周期阻滞在G0/G1期显著抑制细胞增殖，并导致细胞凋亡增加和侵袭抑制。体内研究证实ZFX促进肿瘤生长。机制上，MAPK通路激活参与了ZFX的致癌功能。
ZFX在PCa中作为一种假定的癌基因发挥作用，可能是该疾病的一个新的治疗靶点。
