The Role And Mechanism Of Kinesin Family Members KIF2C/4A/10/11/14/18B/20A/23 In Liver Cancer

Background and Objective:At present,liver cancer is still the fifth most common cancer and the second-ranked tumor-related cause of death worldwide.Hepatocellular carcinoma has the characteristics of high malignancy,high recurrence rate and poor prognosis.Therefore,a better understanding of the underlying pathogenesis and etiology is essential to improve the early diagnosis and treatment of liver cancer.Studies have confirmed that intervention of cell division by disrupting the formation of mitotic spindles is effective in the treatment of tumors.Drugs that target microtubules(MT)such as paclitaxel can disrupt the dynamics of MT and lead to prolonged mitotic arrest time,which eventually leads to cell death.Kinesin superfamily proteins(KIF)are a class of molecular motors.KIF can participate in the transport of organelles,protein complexes and mRNA,and participate in the movement of chromosomes and spindles during mitosis and meiosis,suggesting that KIF be involved in tumorigenesis play an important role in development.However,the role and mechanism of KIF in liver cancer are still unclear.This project will study the expression of KIF in liver cancer,its effect on the prognosis of liver cancer patients,its effect on the proliferation of liver cancer cells,and the related mechanisms of its effects,to clarify the cancer-promoting effect of KIF in liver cancer,and to evaluate the possibility of KIF family molecules as prognostic factors and therapeutic target for liver cancer patients.Methods:The Oncomine database was used to analyze the expression of 45 KIF genes in liver cancer,and the highly expressed KIF genes in liver cancer tissues were selected for subsequent analysis;Based on the TCGA-LIHC data set,the expression of the screened KIF gene in liver cancer tissues was analyzed again using the UALCAN database;Human Protein Atlas was used to analyze the expression of screened KIF proteins in liver cancer tissues;Immunohistochemical experiments were used to verify the expression of KIF protein in liver cancer tissues;Based on the TCGA-LIHC data set,the correlation between the expression of KIF gene and the clinicopathological factors of liver cancer and the prognosis of patients was analyzed;Based on the TCGA-LIHC data set,the risk model of liver cancer patients was constructed,and the ICGC-LIRI-JP data set was used to verify the effectiveness of the risk model;Pathway enrichment analysis showed that KIF molecules may be involved in regulating the signaling pathways of liver cancer;The effects of KIF on proliferation and cell cycle of liver cancer cells were evaluated by flow cytometry clone formation assay;Western blotting experiment was used to verify that KIF molecule can participate in the regulated cell cycle signaling pathway.Results:Based on the Oncomine database,8 of the 45 KIF genes(KIF2C/4A/10/11/14/18B/20A/23)are up-regulated in liver cancer tissues;based on the UALCAN database,Human Protein Atlas and immunohistochemistry experiments,it was further confirmed that the expressions of these 8 KIF mRNA and protein were significantly up-regulated in liver cancer tissues;the risk model constructed by these 8 KIF genes can predict the survival prognosis of liver cancer patients;cell experiments in vitro confirmed that down-regulating the expression of these 8 KIF molecules in liver cancer cells could inhibit the proliferation of liver cancer cells,and confirmed that these 8 KIF molecules were involved in regulating the cell cycle process of liver cancer cells.Conclusion:We determined that KIF2C/4A/10/11/14/18B/20A/23 is up-regulated in liver cancer and promotes the proliferation of liver cancer cells.Importantly,we constructed a new KIF mRNA risk model that is significantly correlated with the survival rate of liver cancer patients.This KIF mRNA risk model can add prognostic value to tumor staging and grading systems,which may help to develop more personalized treatments for liver cancer patients.