Fuction Role Of Ubiquitin-specific Protease 11 In Non-small Cell Lung Cancer

Lung cancer is one of the most common primary p?Lmonary malignant tumors,its' pathological types include small cell lung cancer and non-small cell lung cancer(NSCLC),and NSCLC accounts for 85%to 90%of the total,it causes serious damage to human health.In recent years,the incidence and mortality rate of lung cancer were increasing,and China has the largest number of lung cancer patient in the world.At present,most of the lung cancer treatments are chemotherapy,radiotherapy and surgery.Although the treatment technology of lung cancer has developed fast,the 5-year survival rate is only 10%.Surgery treatment can significantly improve the survival rate of early lung cancer,Chemotherapy is the major treatment for advanced lung cancer,but the drug resistance rate is getting higher with more times of chemotherapy,it's not good for treatment.At present,there is no ideal treatment for advanced lung cancer,so the study of lung cancer pathogenesis and finding the related molec?Lar targets are of great significance to the prevention and control of lung cancer.Ubiquitin-specific protease11(USP11),a member of the deubiquitinating enzyme family,is a cysteine protease.Recent studies have revealed that USP11 can mediate several cell?Lar life process,including DNA damage repair,cell proliferation,cell apoptosis,signal transduction.Meanwhile,USP11 plays an important role in the development and progression of diseases.p21,encoded by CDKN1A,belongs to CIP/KIP family,and it's a protein of the cell cycle inhibitory(CKI).The roles involve cell cycle,differentiation,cell migration,cytoskeletal dynamics,cell?Lar stress response,pluripotent stem cell reprogramming,DNA transcription and repair,cell aging and so on.This research has found that the expression of USP11 is lower in NSCLC tissues than in the adjacent normal NSCLC tissues,and the difference is statistically significant,it showed that USP11 may be associated with the development of NSCLC.In order to find more meaningf?L proteins interacted with USP11,we constructed the FLAG-USP11-HA double labels plasmid.After tandem affinity purification,protein samples were detected by mass spectrum.Based on the scores greater than 10 from mass spectrometry res?Lts,we got 49 kinds of proteins.These proteins are involved in different physiological processes in the cells,such as the metabolism of large molec?Les,the synthesis of compounds,transcription initiation,extention and termination,transcription and expression of virus and life cycle,protein localization,etc.The molec?Lar fuctions include the combination with nucleotide,RNA and poly(A)RNA,constituting the structure of the ribosome,reg?Lating the activity of transcription initiation and some of the molec?Lar structures activities,those provided the basis for the subsequent study.In order to find out the biological function of USP11 in NSCLC,we constructed an usp11 expression vector and lentiviral shRNA specifically against uspll.We performed MTT assay,and found that it was through p21 that uspll overexpression inhibited cell proliferation,and the promotion of cell proliferation that uspll knockdown exhibited was also depended on p21.Tumorigenicity test res?Lts suggested that USP11 knockdown promoted the growth of NSCLC tumor transplanted in nude mice.This study has established the correlation between USP11 and NSCLC clinical pathological tissues,revealed the potential molec?Les interacted with USP11 in cells,and has confirmed that USP11 mediates NSCLC biology function through p21,those findings will lay the foundation for the further study of USP11 in NSCLC.