UHRF1 predicts poor prognosis by triggering cell cycle in lung adenocarcinoma
UHRF1 predicts poor prognosis by triggering cell cycle in lung adenocarcinoma
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UHRF1通过触发肺腺癌细胞周期预测不良预后
DOI：
10.1111/jcmm.15438
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发表时间：
2020-06-03
影响因子：
5.3
通讯作者：
Zhang, Qiuping
中科院分区：
文献类型：
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作者：
Tu, Zhenbo;Deng, Xinzhou;Zhang, Qiuping
越来越多的证据表明，具有植物同源域和环指结构域1的泛素样蛋白(Uhrf1)在非小细胞肺癌(NSCLC)中过表达，但uhrf1在NSCLC亚型中的表达和功能尚不清楚。在这里，我们研究了uhrf1在大型NSCLC队列中的表达和预后特征，并探索了uhrf1上调过程中的分子特征。我们发现uhrf1在肺鳞状细胞癌(SCC)中高表达。令人惊讶的是，上调的uhrf1只与肺腺癌(ADC)的总体生存有关，而uhrf1的下调显著地减弱了ADC的肿瘤形成。我们机械地确定了一个Hub基因，该基因总共包括55个与uhrf1相关的基因，这些基因与细胞周期途径密切相关，导致ADC患者的临床预后较差。此外，我们还观察到uhrf1基因的敲除只影响ADC细胞周期，并诱导细胞凋亡。这些结果表明，上调的uhrf1仅通过触发细胞周期途径促进肺ADC的存活，它可能是肺ADC患者预后的生物标志物。
Accumulating evidence suggests that ubiquitin-like with plant homeodomain and ring finger domains 1 (UHRF1) is overexpressed in non-small cell lung cancer (NSCLC); however, the expression and function of UHRF1 in the subtype of NSCLC are still unclear. Here, we investigate the expression and prognosis traits of UHRF1 in large NSCLC cohorts and explore the molecular characters during UHRF1 up-regulation. We find that UHRF1 is predominantly overexpressed in lung squamous cell carcinoma (SCC). Surprisingly, the up-regulated UHRF1 is only associated with the overall survival of lung adenocarcinoma (ADC) and knockdown of UHRF1 dramatically attenuates ADC tumorigenesis. Mechanically, we identify a hub gene that includes a total of 55 UHRF1-related genes, which are tightly associated with cell cycle pathway and yield to the poor clinical outcome in ADC patients. What's more, we observe knockdown of UHRF1 only affects ADC cells cycle and induces cell apoptosis. These results suggest that up-regulated UHRF1 only contributes to lung ADC survival by triggering cell cycle pathway, and it may be a prognostic biomarker for lung ADC patients.