Study On The Mechanism Of FGF13 Regulating ROS Production And Apoptosis Of A549 Cells

Fibroblast growth factor 13(FGF13)is a member of the fibroblast growth factor family and is expressed in the mammalian brain,skeletal muscle and ovary.The latest research has found that FGF13 is highly expressed in cancer tissues such as cervical cancer,breast cancer and pancreatic cancer,and promotes cancer proliferation,invasion and metastasis.In addition,FGF13 has been found that was highly expressed in lung cancer,and promotes the proliferation and survival of lung cancer cells.But the relationship and mechanism between FGF13 and non-small cell lung cancer(NSCLC)cell apoptosis are still unclear.In this study,the A549 cell line that stably interferes with FGF13 was established,and the differential gene expression after interference with FGF13 was analyzed by transcriptome sequencing.GO and KEGG enrichment analysis was performed to explore the differential genes and related signal pathways that FGF13 may participate in the regulation of A549 cells.The effect and mechanism of FGF13 on the production of reactive oxygen species(ROS)were explored in A549 cells.The effect and molecular mechanism of FGF13 on A549 cell apoptosis were preliminarily explored at the cell and protein level.This study provided a reference for analyzing the biological function of FGF13 in NSCLC.The main results were as follows:1.Two groups of A549 cell lines that stably interfere with FGF13 have been successfully established.Among them,the interference efficiency of FGF13-sh RNA-1group is 90% and 62% at the m RNA and protein levels respectively,which can be used for follow-up research.2.Transcriptome sequencing analysis results found that interference with FGF13 caused the up-regulation of most of the differential genes in A549 cells and affected the gene expression of a variety of cell components.Among them,differential genes are mainly enriched in various processes such as cell proliferation,migration,apoptosis,metabolism and redox.3.FGF13 may regulate the production of ROS by regulating nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4)protein expression and nuclear factor-erythroid2-related factor 2(Nrf2)-mediated antioxidant system in A549 cell.4.Interfering with FGF13 promoted A549 cell apoptosis,and down-regulated the expression of the anti-apoptotic protein B-cell lymphoma-2(Bcl-2),up-regulated the expression of pro-apoptotic protein cysteine aspartic protease-3(Caspase-3)and Cleaved caspase-3,combined with the results of FGF13 regulating production of ROS,indicating that FGF13 may regulate A549 cell apoptosis through the ROS/Caspase-3 pathway.Conclusion: FGF13 may regulate intracellular production of ROS by regulating NOX4 protein expression and Nrf2-mediated antioxidant system,and regulate A549 cell apoptosis through the ROS/Caspase-3 pathway.