KCTD10 Inhibits The Malignant Biological Behavior Of Lung Cancer Cells And Its Molecular Mechanism

Currently,the occurrence rate of lung cancer continues to rise,has become the largest number of cases and deaths of cancer types in China.KCTD10 is a potassium ion tetrameric channel protein belonging to the PDIP1 family with BTB/POZ domains and PCNA binding sites.KCTD10 has been reported to play an important role in early embryonic development and angiogenesis in mice.KCTD10 can interact with subunits of PCNA and DNA polymerase ?,and is related to cell proliferation and cycle,DNA damage and repair.It is regulated by tumor necrosis factor TNF-? and VEGF.The molecular mechanism of KCTD10 in cancer development is relatively few,and the related molecular mechanism in lung cancer is not clear.GEPIA database reveals that the expression of KCTD10 in normal lung tissue was higher than that in lung cancer tissue,and the relationship between KCTD10 expression and patient survival was predicted by Kaplan-meier plotter.The prognosis of patients with high expression of KCTD10 was better than that of patients with low expression of KCTD10.Secondly,the expression of KCTD10 in lung cancer cell line and human umbilical vein endothelial cell line was detected,and A549 cell lines with relatively low expression were selected to construct KCTD10 overexpression stable cell line.We used colony formation and MTT assays to detect the effect of KCTD10 overexpression on cell viability,migration and invasion ability,confirming that KCTD10 can inhibit lung cancer cell growth and decrease the migration and invasion of lung cancer cells.KCTD10 has been shown to inhibit lung cancer in vitro,then we performed subcutaneous tumorigenesis in nude mice.The results showed that the tumor volume and weight in NC group were larger than those in KCTD10 overexpression group,and HE staining showed that the density of tumor cells in KCTD10 overexpression group was less than that in NC group and the cell proportion of abnormal nuclear morphology was lower.The expression of BCL-2,E-cadherin and Vimentin in lung cancer cells was detected.Overexpression KCTD10 could up-regulate the expression of E-cadherin,down-regulate the expression of Vimentin and BCL-2,indicating that KCTD10 is involved in the EMT pathway of inhibiting lung cancer cells.Taken together,our study demonstrated that KCTD10 plays a role in inhibiting malignant biological behavior and EMT progression in lung cancer cells,slowing the development of tumors,which suggests KCTD10 may be a potential target for lung cancer therapy.