PAQR4 promotes cell proliferation and metastasis through the CDK4-pRB-E2F1 pathway in non-small-cell lung cancer
PAQR4 promotes cell proliferation and metastasis through the CDK4-pRB-E2F1 pathway in non-small-cell lung cancer
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DOI：
10.2147/ott.s181432
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发表时间：
2019-01-01
影响因子：
4
通讯作者：
Liu, Rongyu
中科院分区：
文献类型：
--
作者：
Wu, Bin;Liu, Rongyu
背景资料：研究表明，人乳腺癌中存在着adipoQ受体4（adipoQ receptor 4，PAQR 4），但PAQR 4在非小细胞肺癌（non-small-cell lung cancer，NSCLC）中的作用尚不清楚。方法：采用实时荧光定量PCR（qRT-PCR）和免疫组化（IHC）方法检测PAQR 4在HCC组织和癌旁正常组织中的表达，并分析其与NSCLC发生发展的关系。采用MTT法、集落形成实验、流式细胞术（FCM）、创伤愈合实验和transwell侵袭实验观察PAQR 4对细胞增殖、集落形成、细胞周期、迁移和侵袭的影响。结果：PAQR 4基因在NSCLC组织中的表达明显高于正常对照组，PAQR 4基因在NSCLC组织中的表达明显高于正常对照组，PAQR 4基因在NSCLC组织中的表达明显高于正常对照组。此外，我们发现PAQR 4在NSCLC细胞系中也显著上调，与正常人肺上皮细胞相比。此外，我们发现PAQR 4的过表达促进了NSCLC细胞的增殖、集落形成、迁移和侵袭，而PAQR 4的敲低抑制了NSCLC细胞的增殖、集落形成、迁移和侵袭。结论：PAQR 4有可能成为NSCLC治疗的新靶点。
Background: 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.Methods: 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.Results: 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.Conclusion: Hence, these results suggest that PAQR4 may be used as a new target in NSCLC therapy.