Wu Bin, Liu Rongyu
Department of Pulmonary and Critical Care Medicine, Baoan Central Hospital of Shenzhen, Shenzhen 518102, China.
Department of Pulmonary and Critical Care Medicine, First Affiliated Hospital of Anhui Medical University, Hefei 230022, China,
Onco Targets Ther. 2019 May 13;12:3625-3633. doi: 10.2147/OTT.S181432. eCollection 2019.
It is reported that progestin and adipoQ receptor 4 (PAQR4) has a tumorigenic effect on human breast cancer, but the role of PAQR4 in non-small-cell lung cancer (NSCLC) is unknown. The aim of this study was to investigate the role of PAQR4 in NSCLC.
Quantitative real-time PCR (qRT-PCR) and immunohistchemical (IHC) staining were used to analyze the expression of PAQR4 in HCC tissues and adjacent normal tissues. MTT, colony formation assay, flow cytometry (FCM), wound healing assays and transwell invasion assays were used to investigate the effects of PAQR4 on cell proliferation, colony formation, cell cycle, migration and invasion. Murine xenograft model assay was carried out to characterize the effects of PAQR4 knockdown on tumor growth in vivo.
In this study, we found that the expression of PAQR4 was significantly upregulated in the NSCLC tissues of patients compared with that in the matched non-cancerous tissues. In addition, we found that PAQR4 was also significantly up-regulated in the NSCLC cell lines compared with normal human lung epithelial cells. Besides, we found that the over-expression of PAQR4 promoted promoted proliferation, colony formation, migration and invasion of the NSCLC cells, whereas the knockdown of PAQR4 inhibited proliferation, colony formation, migration and invasion of the NSCLC cells. Furthermore, mechanistic studies showed that the CDK4-pRB-E2F1 pathway was involved in NSCLC.
Hence, these results suggest that PAQR4 may be used as a new target in NSCLC therapy.
据报道，孕激素和脂联素受体4（PAQR4）对人类乳腺癌具有致瘤作用，但PAQR4在非小细胞肺癌（NSCLC）中的作用尚不清楚。本研究旨在探讨PAQR4在NSCLC中的作用。
采用定量实时聚合酶链反应（qRT-PCR）和免疫组织化学（IHC）染色分析PAQR4在NSCLC组织及癌旁正常组织中的表达。采用MTT法、集落形成实验、流式细胞术（FCM）、伤口愈合实验和Transwell侵袭实验研究PAQR4对细胞增殖、集落形成、细胞周期、迁移和侵袭的影响。通过小鼠异种移植模型实验来表征敲低PAQR4对体内肿瘤生长的影响。
在本研究中，我们发现与配对的非癌组织相比，PAQR4在NSCLC患者组织中的表达显著上调。此外，我们发现与正常人肺上皮细胞相比，PAQR4在NSCLC细胞系中也显著上调。此外，我们发现PAQR4的过表达促进了NSCLC细胞的增殖、集落形成、迁移和侵袭，而敲低PAQR4则抑制了NSCLC细胞的增殖、集落形成、迁移和侵袭。此外，机制研究表明CDK4-pRB-E2F1通路参与了NSCLC的发生发展。
因此，这些结果表明PAQR4可能作为NSCLC治疗的新靶点。
