Ye Qing, Mohamed Rehab, Dakhlallah Duaa, Gencheva Marieta, Hu Gangqing, Pearce Martin C, Kolluri Siva Kumar, Marsh Clay B, Eubank Timothy D, Ivanov Alexey V, Guo Nancy Lan
WVU Cancer Institute, West Virginia University, Morgantown, WV 26506, USA.
Lane Department of Computer Science and Electrical Engineering, West Virginia University, Morgantown, WV 26506, USA.
Int J Mol Sci. 2021 Apr 4;22(7):3752. doi: 10.3390/ijms22073752.
Our previous study found that zinc finger protein 71 (ZNF71) mRNA expression was associated with chemosensitivity and its protein expression was prognostic of non-small-cell lung cancer (NSCLC). The Krüppel associated box (KRAB) transcriptional repression domain is commonly present in human zinc finger proteins, which are linked to imprinting, silencing of repetitive elements, proliferation, apoptosis, and cancer. This study revealed that had a significantly higher expression than the -less isoform in NSCLC tumors ( = 197) and cell lines ( = 117). Patients with higher expression had a significantly worse survival outcome than patients with lower expression (log-rank = 0.04; hazard ratio (HR): 1.686 [1.026, 2.771]), whereas overall and -less expression levels were not prognostic in the same patient cohort. expression was associated with epithelial-to-mesenchymal transition (EMT) in both patient tumors and cell lines. was overexpressed in NSCLC cell lines resistant to docetaxel and paclitaxel treatment compared to chemo-sensitive cell lines, consistent with its association with poor prognosis in patients. Therefore, isoform is a more effective prognostic factor than overall and -less expression for NSCLC. Functional analysis using CRISPR-Cas9 and RNA interference (RNAi) screening data indicated that a knockdown/knockout of ZNF71 did not significantly affect NSCLC cell proliferation in vitro.
我们之前的研究发现，锌指蛋白71（ZNF71）的mRNA表达与化疗敏感性相关，其蛋白表达可作为非小细胞肺癌（NSCLC）的预后指标。Krüppel相关框（KRAB）转录抑制结构域常见于人类锌指蛋白中，这些蛋白与印记、重复元件沉默、增殖、凋亡和癌症相关。本研究显示，在NSCLC肿瘤（n = 197）和细胞系（n = 117）中，[具体某种形式]的表达明显高于[具体缺失某种形式]的异构体。[具体某种形式]高表达的患者生存结果明显比[具体某种形式]低表达的患者差（对数秩检验P = 0.04；风险比（HR）：1.686 [1.026, 2.771]），而在同一患者队列中，[具体某种形式]的总体表达水平和[具体缺失某种形式]的表达水平均不能作为预后指标。[具体某种形式]的表达与患者肿瘤和细胞系中的上皮-间质转化（EMT）相关。与化疗敏感细胞系相比，[具体某种形式]在对多西他赛和紫杉醇治疗耐药的NSCLC细胞系中过表达，这与其与患者预后不良相关一致。因此，对于NSCLC而言[具体某种形式]异构体是比[具体某种形式]总体表达和[具体缺失某种形式]表达更有效的预后因素。使用CRISPR-Cas9和RNA干扰（RNAi）筛选数据进行的功能分析表明，敲低/敲除ZNF71对体外NSCLC细胞增殖没有显著影响。
