The Role And Mechanism Of KIAA1456 Inhibiting The Proliferation,migration,and Invasion Of Lung Cancer Cells

Part1.The expression of KIAA1456 in lung cancer tissues and its relationship with prognosis of lung cancer patientsObjective:Lung cancer is one of the leading causes of cancer-related deaths worldwide and an important disease threatening human health.When diagnosed with lung cancer,most patients have been in the advanced stage,and the overall treatment of lung cancer is poor.KIAA1456 protein is significantly lower in breast cancer,colon cancer,bladder cancer,cervical cancer and testicular cancer,and is considered as a potential tumor suppressor gene.The expression of KIAA1456 in lung cancer and its relationship with prognosis of lung cancer patients are still unclear.Materials and methods:To observe the expression of KIAA1456 role in lung cancer,immunohistochemical staining was used to evaluate the expression of KIAA1456 in lung cancer tissues and paracancerous tissues.And the association between KIAA1456 and clinicopathological features of lung cancer was analyzed.Kaplan-Meier analysis was used to estimate survival curve of KIAA1456 in lung cancer.Results:The expression of KIAA1456proteinin lung cancertissues was significantly lower than that in paracancerous tissues;the difference was statistically significant(P<0.05).The low expression of KIAA1456 in lung cancer tissues was significantly correlated with pT grade,pN grade,AJCC staging and pathological staging,but not correlated with sex,age,histological type and tumor size of lung cancer patients.Low expression of KIAA1456 is closely related to poor prognosis in lung cancer patients.Conclusion:In conclusion,the low expression of KIAA1456 is significantly correlated with the progression of lung cancer,and can be used as a useful prognostic factor for lung cancer patients.KIAA1456 may be a potential new target for lung cancer treatment.Part2.The mechanism of KIAA1456 inhibiting proliferation,migration and invasion of lung cancer cellsObjective:As a tumor suppressor gene,KIAA1456 has been studied in some human tumors.However,KIAA1456 has not yet been reported on the proliferation,migration and invasion of lung cancer cells.Materials and methods:we first transfected the KIAA1456 overexpression plasmid and the corresponding blank control in lung cancer A549 and GLC-15 cells.The effect of KIAA1456 on the proliferation of lung cancer cells was studied by CCK-8 cell proliferation test;the effect of KIAA1456 on the migration and invasion of lung cancer cells was studied through cell invasion and scratch test.Meanwhile,Western Blot was used to detect the changes of Cyclin D1 and E-cadherin protein in lung cancer cells after KIAA1456 overexpression.Finally,we constructed the KIAA1456 overexpressed A549 cell line(LV-KIAA1456)through the lentivirusand constructed the empty lentivirus as the blank control group(LV-NC).A549 cells stably transfected were injected into the anterior axillary of nude mice to observe the effect of the tumor growth in KIAA1456 lung cancer,and the effect of KIAA1456 on the lung metastasis was observed by tail vein injection with stable cells in nude mice.Finally,Western Blot detected the changes of Cyclin D1 protein in subcutaneous tumor tissues,and detected the change of E-cadherin protein in the metastatic lung tissue.Results:The proliferation tests of CCK-8 cells showed that overexpression of KIAA1456 significantly inhibited the proliferation of A549 and GLC-15 in lung cancer cells,and the cell invasion experiments revealed that forced KIAA1456 expression obviously impaired the invasion ability of lung cancer cells,and the scratch tests showed that overexpression of KIAA1456 significantly inhibited the scar healing of lung cancer cells.Western Blot results showed that KIAA1456 could downregulate the level of Cyclin D1 protein in lung cancer cells and upregulate the protein level of E-cadherin in lung cancer cells.In vivo experiments in nude mice showed that KIAA1456 inhibited the growth of lung cancer and inhibited lung metastasis in lung cancer cells.Conclusion:To sum up,KIAA1456 can inhibit the proliferation of lung cancer cells by down regulation of Cyclin D1 protein,and KIAA1456 can inhibit the migration and invasion of lung cancer cells by up regulation of E-cadherin protein.Therefore,it is speculated that KIAA1456 may be a new target for lung cancer treatment.