Study On The Role And Mechanism Of Deubiquitin Enzyme MINDY-1 In The Development And Progression Of Lung Adenocarcinoma

Background: According to statistics from the World Health Organization,lung cancer is the world’s second highest incidence rate cancer with the highest mortality rate.In2020,there were more than 2.2 million new cases of lung cancer worldwide and nearly1.8 million deaths.Lung cancer is divided into two categories: non-small cell lung cancer and small cell lung cancer,of which non-small cell lung cancer accounts for about 85%.Non-small cell lung cancer is divided into three categories: adenocarcinoma(about 40%),squamous cell carcinoma(25%-30%)and large cell carcinoma(5%-10%).The current methods of treating lung cancer include surgical resection,chemotherapy,targeted therapy,and immunotherapy.Among them,targeted therapy is one of the most promising research methods at present.According to the different gene mutations of lung cancer patients,the use of corresponding targeted drugs can effectively improve the survival of patients,and is less toxic than traditional chemotherapy.And the treatment effect is better.However,there are few targets for targeted therapy,and it is difficult to cover the treatment of all patients under the background of very complicated lung cancer gene mutations.Therefore,exploring more targets is of great significance for the future treatment of lung cancer.This article uses lung adenocarcinoma cell lines model,mouse allograft tumor model and lung adenocarcinoma mouse model to explore the role and mechanism of deubiquitinating enzyme MINDY-1 in lung adenocarcinoma.Objective: To explore the role of deubiquitinating enzyme MINDY-1 in lung adenocarcinoma and its mechanism to affect lung adenocarcinoma,so as to provide a potential therapeutic target for lung adenocarcinoma in the future.Methods: Using bioinformatics methods to preliminarily analyze the mutation frequency and types of MINDY-1 in lung adenocarcinoma,analyze whether the mutation has biological significance in lung adenocarcinoma,and speculate that MINDY-1 is an oncogene or a tumor suppressor gene.According to the results of bioinformatics analysis,MINDY-1/Mindy-1 knockdown,knockout and overexpression cell lines were constructed in lung adenocarcinoma cell lines to explore its physiological functions in lung adenocarcinoma.Further verify its role in lung adenocarcinoma in mouse transplantation tumor model and lung adenocarcinoma model.Finally,the MINDY-1/Mindy-1 knockdown and knockout lung adenocarcinoma cell lines were used to explore the mechanism of its effect on lung adenocarcinoma.Results: First,through bioinformatics analysis,the mutation frequency of MINDY-1 in lung adenocarcinoma patient samples is reach up to 22%,and it is mainly amplified and m RNA expression up-regulated.Based on this,it is speculated that it may be a carcinogenic gene in lung adenocarcinoma.Secondly,MINDY-1 was over-expressed in the human lung adenocarcinoma cell line H1299.The results showed that overexpression of MINDY-1 promoted cell migration and invasion;knocking down MINDY-1 in H1299,cell proliferation and migration ability were affected inhibition.Furthermore,MINDY-1/Mindy-1 knockout cell lines were constructed in H1299 and TDCL(mouse lung adenocarcinoma cell line)cells,and the above experiment was repeated,and the results obtained were consistent that knocking out MINDY-1/Mindy-1 can Inhibit cell proliferation and migration ability.Subsequently,the mouse transplanted tumor model was inoculated with Mindy-1 knockout cell line.The results showed that the growth rate of subcutaneous transplanted tumors after Mindy-1knockout were significantly inhibited compared with the control.In addition,in the mouse lung adenocarcinoma model,the lungs of mice infected with Mindy-1 lentivirus produced more tumors.In summary,the results of cell experiments and mouse model show that Mindy-1 can promote the proliferation of lung cancer cells and the growth of lung tumors.Subsequently,we explored the mechanism of Mindy-1 affecting lung adenocarcinoma.Western blot was used to search for signal pathways related to tumorigenesis and development that are affected by Mindy-1 knockdown/knockout.It was found that the expression of phospho-JNK was up-regulated,and the level of phospho-c-Jun was also up-regulated after Mindy-1 knockdown/knockout.Therefore,preliminary results show that Mindy-1 affects the development of lung adenocarcinoma by regulating the JNK signaling pathway.Conclusion: The deubiquitinating enzyme MINDY-1 act as an oncogene in lung adenocarcinoma.Knockout of MINDY-1 can inhibit the occurrence and development of lung adenocarcinoma.MINDY-1 may affect the occurrence and development of lung adenocarcinoma by regulating the JNK signaling pathway.