Molecular Analysis of ZNF71 KRAB in Non-Small-Cell Lung Cancer.
Molecular Analysis of ZNF71 KRAB in Non-Small-Cell Lung Cancer.
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非小细胞肺癌中ZNF71 KRAB的分子分析
DOI：
10.3390/ijms22073752
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发表时间：
2021-04-04
影响因子：
5.6
通讯作者：
Guo NL
中科院分区：
文献类型：
--
作者：
Ye Q;Mohamed R;Dakhlallah D;Gencheva M;Hu G;Pearce MC;Kolluri SK;Marsh CB;Eubank TD;Ivanov AV;Guo NL
我们前期研究发现锌指蛋白71（ZNF 71）mRNA表达与非小细胞肺癌（NSCLC）化疗敏感性相关，其蛋白表达与NSCLC的预后有关。Krüppel相关盒（KRAB）转录抑制结构域通常存在于人类锌指蛋白中，其与印记、重复元件沉默、增殖、凋亡和癌症有关。该研究显示，ZNF 71 KRAB在NSCLC肿瘤（n = 197）和细胞系（n = 117）中的表达显著高于ZNF 71 KRAB-less亚型。ZNF 71 KRAB高表达患者的生存结局显著差于ZNF 71 KRAB低表达患者（对数秩p = 0.04;风险比（HR）：1.686 [1.026，2.771]），而ZNF 71总体和KRAB低表达水平在同一患者队列中不具有预后性。ZNF 71 KRAB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，ZNF 71 KRAB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的相关性一致。因此，ZNF 71 KRAB亚型是比ZNF 71总体和KRAB低表达的NSCLC更有效的预后因子。使用CRISPR-Cas9和RNA干扰（RNAi）筛选数据的功能分析表明，ZNF 71的敲低/敲除在体外不会显著影响NSCLC细胞增殖。
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 ZNF71 KRAB had a significantly higher expression than the ZNF71 KRAB-less isoform in NSCLC tumors (n = 197) and cell lines (n = 117). Patients with higher ZNF71 KRAB expression had a significantly worse survival outcome than patients with lower ZNF71 KRAB expression (log-rank p = 0.04; hazard ratio (HR): 1.686 [1.026, 2.771]), whereas ZNF71 overall and KRAB-less expression levels were not prognostic in the same patient cohort. ZNF71 KRAB expression was associated with epithelial-to-mesenchymal transition (EMT) in both patient tumors and cell lines. ZNF71 KRAB 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, ZNF71 KRAB isoform is a more effective prognostic factor than ZNF71 overall and KRAB-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.
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影响因子：
10.5
作者：
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通讯作者：
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通讯作者：
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