Study On The Function And Clinical Significance Of Tryptophan-tRNA Synthetase 1 In Serous Ovarian Cancer

Objective:Ovarian cancer(OC)is one of the most common gynecologic cancer a malignant tumor,because the insidious onset,the lack of sensitive and specific tumor marker,the majority of patients diagnosed has entered advanced,and the incidence is rising in recent years,and after surgery There are still some recurrences after chemotherapy treatment,and the pathogenesis is still unclear.It has been reported that amino-tRNA synthetase(ARS)proliferation of the cancer,invasion and prognosis,wherein tryptophyl-tRNA synthetase WARS1 plays an important role in the proliferation of cancer cells.This study aims to observe the effect of WARS1 on the biological functions of ovarian cancer cells and the study of specific molecular mechanisms through bioinformatics analysis and in vitro experiments.Method:(1)Databases analysis were used to detect the expression of WARS1 in serous ovarian cancer tissues and it was positively correlated with poor prognosis expression of early ovarian cancer;Immunohistochemical staining showed expression WARS1 was significantly higher in serous ovarian cancer tissues than benign serous cystadenoma tissues,and its expression and clinical staging of serous ovarian cancer,is closely related to lymph node metastasis.(2)The function of WARS1 on the proliferation of serous ovarian cancer cells by CCK-8 assay and clone formation assay;Transwell assay was used to study the effect of WARS1 on the migration and invasion of serous ovarian cancer cells;flow cytometry was used to study the effect of WARS1 on the apoptosis of serous ovarian cancer cells.(3)The high-throughput sequencing results of ovarian cancer tissues in the TCGA database were used for gene set enrichment analysis(GSEA),and the molecular mechanism of WARS1 promoting the development of ovarian cancer was explored,and it was initially verified by Western Blot experiments.Results:(1)The results of database analysis showed that WARS1 expression was significantly higher in epithelial ovarian cancer,and it was positively correlated with poor prognosis expression of early ovarian cancer;rian cancer.The results of immunohistochemistry showed that WARS1 was highly expressed in serous ovarian cancer and was closely related to the pathological grade and clinical stage of serous ovarian cancer.(2)The results of CCK-8 assay and clone formation assay showed that silencing WARS1 significantly inhibited the proliferation of serous ovarian cancer cells;Transwell assay was used to study the effect of WARS 1 on the migration and invasion of serous ovarian cancer cells;flow cytometry was used to study the effect of WARS 1 on the apoptosis of serous ovarian cancer cells.(3)GSEA analysis showed enrichment WARS1 may play a role in tumor promotion by affecting the PI3K/AKT/mTOR pathway.(4)Western Blot results showed that after knocking down WARS1,the expression of p-AKT,p-mTOR,and p-4EBP1 decreased significantly,while the expression of AKT,mTOR,and 4EBP1 did not change significantly.Conclusion:(1)WARS1 significantly higher expression in serous ovarian cancer,and its high expression is associated with early stage ovarian cancer patients with poor prognosis,therapeutic WARS1 is expected to become a new target for serous ovarian cancer.(2)WARS1 promote proliferation serous ovarian cancer cell migration and invasion,the ability to inhibit apoptosis.(3)WARS1 may promote the development of ovarian cancer by activating phosphorylation of AKT/mTOR/4EBP1 signaling pathway.Figure[17]table[6]reference[40].