CARMA3 Transcriptional Regulation Of STMN1 By NF-kappaB Promotes Renal Cell Carcinoma Proliferation And Invasion

Introduction: Renal clear cell carcinoma(cc RCC)is a common lethal malignant tumor.The development of cc RCC is often hidden,leading to delays in surgery.Due to resistance to chemotherapy or radiotherapy,the treatment of advanced cc RCC remains a challenge.Drugs such as sunitinib that act on protein receptor tyrosine kinases(RTKs)have played an important role in the treatment of cc RCC,but these tumors often resist treatment and continue to progress.Although immunotherapy has recently been used as a second-line regimen,the efficiency of immune cell reactivation is still unclear,so its efficiency is unstable.Therefore,cc RCC treatment urgently needs more effective treatment options and new targets.CARMA3 express in tumor cell,and promote both cell proliferation and metastasis.CARMA3 can activate the NF-κB pathway in response to RTKs,thereby promoting the expression of a series of downstream oncogenes.Therefore,CARMA3 may be a potential therapeutic target in cc RCC.Methods: Real-time quantitative PCR was used to detect the expression level of CARMA3 in cc RCC tissues and cells,and the effect of CARMA3 on cell function such as proliferation and metastasis was verified in cc RCC cells.Discover the potential downstream regulatory molecules of CARMA3 from the previous sequencing data and verify them by real-time quantitative PCR and western blotting.Use NF-κB inhibitor,luciferase and Ch-IP to confirm the specific mechanism of CARMA3 on STMN1.Real-time quantitative PCR was used to detect the expression level of STMN1 in cc RCC tissues and cells,and to verify its effect on proliferation and metastasis,and its recovery effect on CARMA3.To further determine the effect of CARMA3-STMN1 on the EMT function of cc RCC cells and its effect on the drug resistance of cc RCC cells.At the same time,the cell co-culture method was used to determine the role of CARMA3 in the immune microenvironment of cc RCC.Results: The expression of CARMA3 at the transcriptional level increased in cc RCC tissues and cells,and CARMA3 can promote proliferation in cc RCC cells.CARMA3 can regulate the expression of STMN1 through NF-κB.The expression level of STMN1 in cc RCC tissues increases,and it can promote proliferation in cc RCC cells.It is verified by the recovery experiment that STMN1 can recover the proliferation inhibition effect caused by CARMA3 knockdown on cell proliferation.CARMA3-STMN1 can affect the invasion and migration ability of cc RCC cells.CARMA3-STMN1 can affect the EMT level of cc RCC cells and the drug resistance of cisplatin.CARMA3 is related to the tumor microenvironment of cc RCC.CARMA3 can affect the interaction between cc RCC and immune cells by co-cultivating with immune cells.Conclusion: CARMA3 is highly expressed in cc RCC tissues and cells,and it can transcriptionally regulate STMN1 expression by activating the NF-κB pathway to promote the proliferation of cc RCC cells.CARMA3-STMN1 can affect the invasion and migration ability of cc RCC cells.At the same time,CARMA3-STMN1 can affect the EMT level of cc RCC cells and the drug resistance of cisplatin.CARMA3 has a certain correlation with immune cell fatigue in the cc RCC tumor microenvironment,and can affect the function of CD4+ T cells.