Underlying Mechanism Of PCYT1A In Proliferation And Migration Of Lung Adenocarcinoma

Lung cancer,around the world,is considered as one of most common malignant cancer.Non-small cell lung cancer(NSCLC),particularly the lung adenocarcinoma is the main cause of cancer-associated death.NSCLC accounts about 85% among all lung cancers,and lung adenocarcinoma accounts most.Cancer cells display infinite proliferation capacity and distant metastasis capacity,and then preserve the malignant biological behaviors of lung cancer.In recent years,the emergence of immunotherapy has significantly improved the survival of patients in advanced lung cancer patients.Targeted PD-L1 / PD-1 inhibitors such as babolizumab,navulizumab,and duvarizumab,combined with chemotherapy,have brought new hope to patients with advanced lung cancer.Due to the individual differential expression of PD-L1 / PD-1 and the easy emergence of drug resistance,the efficacy of targeted therapy for lung cancer is limited.It is urgent to find new targets for lung cancer treatment.PCYT1A,a rate-limiting enzyme of phosphatidylcholine,an important component of Kennedy pathway,has been certified to closely related to cone-rod dystrophy(SMD-CRD),independent retinal dystrophy and lipodystrophy.PCYT1 A has been reported to be associated with tumor progression.In diffuse large B-cell lymphoma,PCYT1 A expression is up-regulated and positively correlated with MYC expression.MYC transcriptional activation of PCYT1 A prevents autophagy which is dependent on necrosis of lymphoma cells,indicating that PCYT1 A may be one of the markers for the progression of diffuse large B-cell lymphoma.In patients with lung squamous cancer and head and neck squamous cell carcinoma,patients with overexpression of PCYT1 A owns a longer disease-free progression(DFS)and the overall survival(OS),suggesting a good prognosis.However,it is still unclear how PCYT1 A played a relevant role in this tumors,and there are a few relevant reports on the role and mechanism of PCYT1 A in other tumors.Therefore,the study on the role of PCYT1 A in specific tumor types and the explanation of its mecha-nism are of great significance to further improve the prognosis of patients,and then provide a theoretical basis for finding new therapeutic targets.In this article,we conducted experiments including antivirus infection,qRTPCR,Western Blot,CCK8 cell proliferation assay,cell colony formation assay,Transwell migration assay,co-immunoprecipitation,immunohistochemistry;Relationship of PCYT1 A and prognosis of patients was analyzed through GEPIA database.We divided our research into three parts to discuss the role of PCYT1 A and its underlying mechanism in lung adenocarcinoma: the first part was conducted to find out what effects PCYT1 A has on proliferation and metastasis in lung adenocarcinoma;The second part studied on the specific mechanism of PCYT1 A affecting the proliferation and metastasis of lung adenocarcinoma.The third part analyzed the relationship between the expression of PCYT1 A and the prognosis of lung cancer patients.We reached the following experimental results:1.PCYT1 A was associated with proliferation and migration in lung adenocarcinoma;2.Study on the mechanism of PCYT1 A in the malignant biological behavior showed that the low expression of PCYT1 A activated the mTORC1 signaling pathway,thus promoting the proliferation and metastasis of LUAD cells.3.Rrelationship between the expression of PCYT1 A and the prognosis was analyzed of 962 lung cancer patients through the GEPIA database,and the expression of PCYT1 A and phosphorylated S6 in clinical samples were also detected.We found that PCYT1 A negatively regulated mTORC1 signaling pathway,indicating a better prognosis in the high-expression group.Based on these studies,we reached to the conclusion: 1.PCYT1 A suppresses the proliferation and migration of lung adenocarcinoma;2.PCYT1 A negatively regulated mTORC1 signaling pathway;3.PCYT1 A high expression shows good prognostic value for lung adenocarcinoma patients.We firstly revealed the role of PCYT1 A in lung adenocarcinoma,as well as its underlying mechanism,providing an experimental basis for further studies on the role of PCYT1 A in the treatment of lung cancer and other types of tumors.