PAQR3 Inhibits Non-small Cell Lung Cancer Growth by Regulating the NF-κB/p53/Bax Axis.
PAQR3 Inhibits Non-small Cell Lung Cancer Growth by Regulating the NF-κB/p53/Bax Axis.
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DOI：
10.3389/fcell.2020.581919
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发表时间：
2020
影响因子：
5.5
通讯作者：
Xu G
中科院分区：
文献类型：
--
作者：
Guo Q;Ke XX;Fang SX;Gao WL;Song YX;Chen C;Lu HL;Xu G
在多发性肿瘤中，脂肪素和脂肪Q受体3（PAQR 3）的表达普遍下调，这与肿瘤进展和不良预后相关。使用各种数据库并在60例非小细胞肺癌（NSCLC）患者中分析PAQR 3的临床价值。此外，使用细胞计数试剂盒-8（CCK-8）、集落形成和流式细胞术测定来评估PAQR 3对NSCLC细胞体外生长的影响。进行基因集富集分析（GSEA）来研究PAQR 3参与肺癌进展的可能机制。并采用蛋白质印迹法验证了相关机制。PAQR 3在60例NSCLC患者中表达降低，且与NSCLC的组织学类型、淋巴结转移、肿瘤大小及诊断有关。PAQR 3表达增加的肺腺癌患者倾向于具有更好的预后。此外，PAQR 3抑制NSCLC细胞的增殖、克隆形成和周期转换，但诱导凋亡。GSEA结果显示PAQR 3通过影响细胞周期、DNA复制和p53信号通路来调控肺癌的进展。我们证实PAQR 3过表达抑制NF-κB的表达，同时增加p53、磷酸化p53和Bax的表达。相反，PAQR 3抑制在这些蛋白中起相反的作用。PAQR 3通过NF-κB/P53/Bax信号通路抑制NSCLC细胞的生长，可能成为NSCLC诊断和治疗的新靶点。
The expression of progestin and adipoQ receptor 3 (PAQR3) is generally downregulated in multiple tumors, which is associated with tumor progression and poor prognosis. The clinical value of PAQR3 was analyzed using various databases and in 60 patients with non-small cell lung cancer (NSCLC). In addition, cell counting kit-8 (CCK-8), colony formation, and flow cytometry assays were used to evaluate the effect of PAQR3 on the growth of NSCLC cells in vitro. Gene set enrichment analysis (GSEA) was performed to investigate the possible mechanism through which PAQR3 is involved in the progression of lung cancer. Furthermore, western blotting was employed to verify the relevant mechanism. The expression of PAQR3 was decreased in 60 NSCLC patients and was related to the histological subtype, lymph node metastasis, tumor size, and diagnosis of NSCLC. Patients with lung adenocarcinoma with increased PAQR3 expression tended to have a better prognosis. Besides, PAQR3 inhibited proliferation, clone formation, and cycle transition in NSCLC cells, but induced apoptosis. The results of GSEA showed that PAQR3 regulated the progression of lung cancer by affecting cell cycle, DNA replication, and the p53 signaling pathway. We confirmed that PAQR3 overexpression inhibited the expression of NF-κB, while it increased the expression of p53, phospho-p53, and Bax. On the contrary, PAQR3 inhibition played an opposite role in these proteins. PAQR3 inhibited the growth of NSCLC cells through the NF-κB/P53/Bax signaling pathway and might be a new target for diagnosis and treatment.
DOI：
10.3779/j.issn.1009-3419.2017.04.06
发表时间：
2017-04-20
期刊：
Zhongguo fei ai za zhi = Chinese journal of lung cancer
影响因子：
--
作者：
Liang X;Sun B;Han J;Zhao X;Liu Z
通讯作者：
Liu Z