| Fibroblast growth factors(FGFs)play an important role in regulating cell proliferation,differentiation and apoptosis.It also participates in the process of tissue development and regeneration.Fibroblast growth factor 13(FGF13)is a member of the fibroblast growth factor subfamily.In recent years,it has been found that the expression is up-regulated in a variety of malignant tumors.However,the role and molecular mechanism of non-small cell lung cancer(NSCLC)remain to be clarified.In this study,the effects of FGF13 and SHCBP1 on the proliferation of A549 cells and their molecular regulatory mechanisms were investigated.In this study,we found that FGF13 was highly expressed in A549 cells,suggesting that FGF13 may be involved in the proliferation of A549 cells.Therefore,CCK-8,plate cloning and immunofluorescence assay were used to detect cell proliferation.The results showed that down-regulation of the expression of FGF13 could significantly inhibit the proliferation of A549 cells,whereas over-expression of FGF13 resulted in the opposite effect.At the same time,down-regulation of the expression of FGF13 significantly reduced the positive rate of Ki67 protein in A549 cells.These results confirm that FGF13 is closely related to the proliferation of A549 cells.In addition,the interference of FGF13 led to cell cycle arrest in G1/S phase of A549 cells.Conversely,over-expression of FGF13 promotes G1/S phase transition in A549 cell cycle.It was found that the cell cycle arrest induced by FGF13 was related to the expression of CyclinE,CDK2,P21 and P27 by detecting G1/S phase related proteins.On the other hand,FGF13 promotes the proliferation of A549 cells by activating AKT/gsk3α/gsk3β signaling pathway.Previous studies have shown that SHC SH2 domain connexin 1(SHCBP1)is up-regulated in a variety of cancer tissues and is involved in the development of cancer.Combined with the results of yeast two-hybrid in our laboratory,it was speculated that there might be interaction between FGF13 and SHCBP1.Therefore,indirect immunofluorescence co-localization and immunoprecipitation experiments confirmed the interaction between FGF13 and SHCBP1.To further detect the effect of SHCBP1 on the proliferation of A549 cells.The results showed that there was no significant change in A549 cell viability and Ki67 protein expression after SHCBP1 overexpression.These results suggest that the up-regulation of SHCBP1 expression has no significant effect on the proliferation of A549 cells.However,the expression levels of P21,P27 and CyclinE1 were significantly different after the interaction of FGF13 and SHCBP1.Moreover,FGF13 plays a better role in promoting cell proliferation when SHCBP1 is overexpressed.In summary,this study elucidated the relationship between FGF13 and proliferation of A549 cells.The possible signaling pathways and molecular mechanisms of FGF13 promoting cell proliferation were analyzed.To clarify the interaction between FGF13 and SHCBP1,it also regulated the proliferation of A549 cells.Provide theoretical and experimental basis for FGF13 as a clinical diagnosis and targeted therapy for NSCLC. |