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HPRT promotes proliferation and metastasis in head and neck squamous cell carcinoma through direct interaction with STAT3
Experimental Cell Research ( IF 3.3 ) Pub Date : 2020-12-21 , DOI: 10.1016/j.yexcr.2020.112424
Lin Wang , Yupu Wang , Nannan Han , Xu Wang , Min Ruan

Increasing effort has been put into finding novel molecular pathways to improve the efficiency of EGFR inhibitors against head and neck squamous cell cancer (HNSCC). In this study, we performed data mining and bioinformatically analysed RNA-Seq data downloaded from TCGA and confirmed that higher expression of HPRT in HNSCC tissue was related to poor prognosis of patients. Then, we conducted in vitro and in vivo loss- and gain-of-function experiments to demonstrate the role of HPRT in HNSCC cell lines. Overexpression of HPRT increased the gene expression of epithelial mesenchymal transition markers via direct interaction with STAT3. Knocking down HPRT significantly decreased tumour growth and enhanced the anticancer effect of EGFR inhibitors against HNSCC xenografts. In conclusion, HPRT is a binding partner of STAT3 that promotes EMT and proliferation. Our findings support HPRT as a promising prognostic indicator and potential therapeutic target for HNSCC.



中文翻译:

HPRT通过与STAT3直接相互作用促进头颈部鳞状细胞癌的增殖和转移

已经投入了更多的努力来寻找新的分子途径来提高EGFR抑制剂对抗头颈部鳞状细胞癌(HNSCC)的效率。在这项研究中,我们进行了数据挖掘,并对从TCGA下载的RNA-Seq数据进行了生物信息学分析,并证实HPRT在HNSCC组织中的较高表达与患者预后不良有关。然后,我们进行了体外体内功能丧失和功能获得实验,以证明HPRT在HNSCC细胞系中的作用。HPRT的过表达通过与STAT3的直接相互作用而增加了上皮间充质转化标志物的基因表达。降低HPRT可以显着降低肿瘤生长并增强EGFR抑制剂对HNSCC异种移植物的抗癌作用。总之,HPRT是STAT3的结合伴侣,可促进EMT和增殖。我们的发现支持HPRT作为HNSCC的有希望的预后指标和潜在的治疗靶标。

更新日期:2020-12-21
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