JMJD8 Promotes Non-small Cell Lung Cancer Proliferation And Invasion By Facilitating The Stability Of EGFR

Lung cancer is currently the fastest-growing malignant tumor.Its morbidity and mortality rank first among Chinese cancers.It poses a major threat to global human health.Therefore,comprehensive policies for targeted prevention,early detection and treatment are needed to control the growing burden caused by cancer.JMJD8 is a Jmj C domain-containing protein that has not been widely examined,despite its potential role in malignant tumor development.The underlying biological functions and molecular mechanisms of JMJD8 in non-small-cell lung cancer(NSCLC)remain unclear.Objective: Previous studies have shown that JMJD8 can promote NF-?B signaling and apoptosis in H293 T cells induced by tumor necrosis factor(TNF).In addition,knockdown of JMJD8 expression inhibited the invasion ability of squamous cell carcinoma cells and affected the viability of DU145 cells.However,its molecular mechanism is still blurry.In this study,examining the expression of JMJD8 in lung cancer tissues and its relationship with the prognosis and clinicopathological characteristics of lung cancer patients.Investigating the potential functions and molecular mechanisms of JMJD8 in lung cancer.Methods: We analyzed the relationship between expression of JMJD8 and its clinicopathological characteristics in 169 tissue samples.We investigated its effect on the proliferation and invasion of lung cancer cells non-small cell lung cancer cells A549 and H1299 after up-regulating / down-regulating the expression of JMJD8,including MTT,colony formation assay and Transwell assay,and explore the relationship between JMJD8 and signal pathway activation in NSCLC by using immunoblotting.Then the endogenous co-immunoprecipitation assay was used to detect the relationship between EGFR and JMJD8 in A549 and H1299 cells,and the effect of JMJD8 on the degradation rate of EGFR was detected by immunoblotting.Results:1.The expression level of JMJD8 in lung tissues was higher than that in normal lung tissues.There is a correlation between the expression of JMJD8 and clinicopathology.The expression of JMJD8 is related to the degree of differentiation of non-small cell lung cancer,tumor size,TNM stage,and there is a correlation with prognosis.2.Decreasing the expression of JMJD8 in non-small cell lung cancer can significantly inhibit the proliferation and invasion of tumor cells.Overexpression of JMJD8 has the opposite effect.3.Overexpression of JMJD8 in non-small cell lung cancer cells can significantly upregulate the expression of cell cycle progression-related proteins,invasion-related proteins,EMT-related proteins,and activate the PI3 K / AKT signaling pathway.Interference with JMJD8 has the opposite effect.4.After over-expression of JMJD8 in non-small cell lung cancer cells,the expression of EGFR also increased.Co-immunoprecipitation showed that JMJD8 interacted with EGFR.5.Further research found that JMJD8 can promote the stability of EGFR.After interfering with JMJD8,the degradation rate of EGFR increased significantly.Overexpression of JMJD8 gave the opposite result.Conclusion: 1.JMJD8 is mainly located in the cell cytoplasm;it is highly expressed in non-small cell lung cancer tissues and is associated with poor prognosis in patients with lung cancer.2.JMJD8 enhances the proliferation of non-small cell lung cancer cells by promoting the expression of Cyclin B1 and CDK1.3.JMJD8 enhances the invasion ability of non-small cell lung cancer cells by promoting the expression of MMP9 and Rho A.4.JMJD8 promotes the malignant behavior of non-small cell lung cancer by activating the PI3 K / AKT signaling pathway and the EMT pathway.5.JMJD8 interacts with EGFR in non-small cell lung cancer cells and increases the stability of EGFR.