HEATR3 Gene Affects The Proliferation,migration And Invasion Of Bladder Cancer Through The AKT/ERK Pathway

Background: Bladder cancer is a relatively common malignant tumor worldwide.The incidence and mortality of urological cancer patients rank first in China.At present,although the diagnosis and treatment technology of bladder cancer has made great progress,its susceptibility to recurrence has caused the incidence and mortality of bladder cancer to continue to rise.Therefore,exploring molecular targets and molecular mechanisms of bladder cancer will help its early diagnosis and targeted therapy,thereby reducing the incidence and mortality.HEATR3(HEAT Repeat Containing 3)is located on chromosome 16q12.1,and its encoded protein plays an important role in ribosomal protein transport and 5S ribonucleoprotein particle(5S RNP)assembly.TCGA database found that HEATR3 expression was upregulated in bladder cancer,suggesting that it may play a pro-cancer role in the occurrence of bladder cancer,but the specific function has not been studied.Additionally,studies have reported that the phosphorylation levels of AKT and ERK were significantly increased in various malignant tumors,including bladder cancer.After their activation,they regulate the occurrence and development of malignant tumors by regulating downstream molecules.Some drugs also treat bladder cancer by inhibiting the AKT and ERK signaling pathways.Therefore,this subject aims to explore the biological function of HEATR3 gene in bladder cancer,and to preliminary explore whether this gene can affect the occurrence and development of bladder cancer through the AKT/ERK signaling pathway.Research methods: 1.Using TCGA database to analyze the expression and prognosis of HEATR3 in bladder cancer.Immunohistochemistry,western blot and q RT-PCR experiments were used to detect the expression of HEATR3 in bladder cancer tissues and cells.2.After down-regulating HEATR3 gene expression in bladder cancer,CCK8 experiment was used to detect cell proliferation and flow cytometry to analyze cell cycle and apoptosis.3.After down-regulating the expression of HEATR3 in bladder cancer,the scratch migration test and transwell test were used to detect cell migration and invasion ability,respectively.Western Blot assay was used to detect the effect of down-regulation of HEATR3 on the expression of AKT and ERK proteins and their phosphorylation levels in bladder cancer cells.Result: 1.Through TCGA database analysis,we found that the expression of HEATR3 gene was significantly up-regulated in bladder cancer,and the expression level of HEATR3 gene was significantly related to the prognosis of bladder cancer.Immunohistochemistry,Western blot and q RT-PCR experiments confirmed that HEATR3 expression was significantly upregulated in bladder cancer tissues and cells.2.The down-expression of HEART3 gene in bladder cancer can inhibit the proliferation,promote the apoptosis ability,and block the cell cycle.3.The down-expression of HEART3 gene in bladder cancer can reduce the migration and invasion ability of bladder cancer cells,without changing the expression of AKT and ERK protein,but reducing the phosphorylation level of AKT and ERK.Conclusion: In summary,this study found that HEATR3 acts as a cancer-promoting factor in the occurrence and development of bladder cancer,which may regulate the AKT and ERK signaling pathways by affecting the phosphorylation levels of AKT and ERK proteins,thereby affecting the proliferation,migration and invasion ability of bladder cancer cells.This result will help to further find new tumor markers and molecular therapeutic targets related to bladder cancer,and provide a theoretical basis for the early diagnosis and treatment of bladder cancer.