期刊
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
卷 8, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2020.581919
关键词
non-small cell lung cancer; PAQR3; prognosis; GSEA; tumor growth
资金
- National Natural Science Foundation of China [81960532]
- Guizhou Provincial Health and Construction Commission
Background The expression of progestin and adipoQ receptor 3 (PAQR3) is generally downregulated in multiple tumors, which is associated with tumor progression and poor prognosis. Methods 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 cellsin 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. Results 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-kappa B, while it increased the expression of p53, phospho-p53, and Bax. On the contrary, PAQR3 inhibition played an opposite role in these proteins. Conclusion PAQR3 inhibited the growth of NSCLC cells through the NF-kappa B/P53/Bax signaling pathway and might be a new target for diagnosis and treatment.
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