Guo Qiang, Ke Xi-Xian, Fang Shi-Xu, Gao Wei-Long, Song Yong-Xiang, Chen Cheng, Lu Hong-Ling, Xu Gang
Department of Thoracic Surgery, The Affiliated Hospital of Zunyi Medical University, Zunyi, China.
Department of Cardiac Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
Front Cell Dev Biol. 2020 Oct 6;8:581919. doi: 10.3389/fcell.2020.581919. eCollection 2020.
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 . 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.
孕激素和脂联素受体3（PAQR3）的表达在多种肿瘤中普遍下调，这与肿瘤进展和不良预后相关。
利用各种数据库并对60例非小细胞肺癌（NSCLC）患者分析PAQR3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检测来评估PAQR3对NSCLC细胞生长的影响。进行基因集富集分析（GSEA）以研究PAQR3参与肺癌进展的可能机制。此外，采用蛋白质印迹法验证相关机制。
60例NSCLC患者中PAQR3表达降低，且与组织学亚型、淋巴结转移、肿瘤大小及NSCLC诊断相关。PAQR3表达增加的肺腺癌患者预后往往较好。此外，PAQR3抑制NSCLC细胞的增殖、克隆形成和细胞周期转变，但诱导细胞凋亡。GSEA结果显示，PAQR3通过影响细胞周期、DNA复制和p53信号通路来调节肺癌进展。我们证实PAQR3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，PAQR3抑制对这些蛋白质起相反作用。
PAQR3通过NF-κB/P53/Bax信号通路抑制NSCLC细胞生长，可能是诊断和治疗的新靶点。
