PYCR1 Promotes Proliferation, Invasion and Drug-Resistance of Lung Cancer Cells by Regulating STAT3-Mediated PI3K/AKT and NF-κB Signaling Pathway

Abstract Background: Aberrant expression of PYCR1 has been proved to be one of the most pivotal regulators of tumor progress and metastasis. However, the detailed role of PYCR1 in promotion of NSCLC progress is not investigated thoroughly. The present study was aimed to thoroughly investigate the effect of PYCR1 in the growth of NSCLC and the underlying mechanisms, so that provide valuable theoretical basis for efficient treatment of NSCLC. Methods: The expressions of PYCR1 and its target genes and downstream signals were respectively determined by Western-blot assay and RT-qPCR experiment. Cell growth of NSCLC cells was investigated using the CCK-8 kit while the proliferation assay was performed with the help of EDU staining. The NSCLC-bearing mice mode was established to evaluate the effect of PYCR1 on the progress of NSCLC and the underlying mechanisms in vivo.Results: It was firstly demonstrated that the PYCR1 was overexpressed in lung cancer tissues and cells and overexpression of PYCR1 contributed to significantly enhanced proliferation, invasion, and drug-resistance of cancer cells and progress of NSCLC tissues. Further studies revealed that up-regulation of PYCR1 level resulted to the elevation of bioactivity of STAT3. Additionally, the positive correlation between the expression of PYCR1 and STAT3 indicated that the PYCR1 promotes the growth of NSCLC through targeting regulation the STAT3 levels. Furthermore, activation of STAT3 by PYCR1 was proved to be able of awaking the PI3K/AKT and NF-κB signaling pathway, which was extremely important to the metabolism, proliferation, cell survival, and growth of many cancer cell types.Conclusion: In conclusion, our study demonstrated that PYCR1 was specifically overexpressed in lung cancer and closely related to rapid progress and drug-resistance thorough regulating the STAT3-mediated PI3K/AKT and NF-κB signaling pathway. It may provide a valuable strategy for treatment of malignant lung cancer.