Expression Of ARID1A In Nasopharyngeal Carcinoma And Its Effect On Malignant Biological Behavior Of Nasopharyngeal Carcinoma Cells

Nasopharyngeal carcinoma(NPC)is a common head and neck malignant tumor in southern China,North Africa and Southeast Asia,with an incidence rate of up to 0.2%.The etiology of the development and progression of NPC may be closely related to geographic areas,genetic factors,environmental factors and Epstein–Barr virus(EBV)infection.Although the treatment of NPC has improved greatly in recent years,the rate of distant metastasis is as high as 14.1%.it will be the key to improve the survival rate of nasopharyngeal cancer patients to explore the molecular mechanism of metastasis and recurrence of nasopharyngeal carcinoma and find effective treatment.AT-rich interactive domain containing protein 1A(ARID1A)is a family member of the switch/sucrose nonfermentable(SWI/SNF)chromatin remodeling complex.ARID1 A was widely recognized as a potential tumor suppressor gene and has been shown to be mutated frequently in endometria-associated cancers,gastric cancer,pancreatic cancer and breast cancer.ARID1 A mutations were closely related to the PI3K/Akt signaling pathway,and ARID1 A mutations were usually associated with PI3K/Akt tsignaling pathway activation.So far,the effect of ARID1 A on nasopharyngeal cancer has not been reported.Objective: In this study,we aimed to detect the expression of ARID1 A in nasopharyngeal carcinoma cell lines,nasopharyngeal carcinoma and normal nasopharyngeal mucosa,and its influence on the biological behavior of nasopharyngeal carcinoma cells and related mechanisms.Methods: 1.Immunohistochemistry detected the expression of ARID1 A in nasopharyngeal carcinoma and normal nasopharyngeal mucosa;fluorogenic quantitative PCR and Western Blot detected the expression of ARID1 A in nasopharyngeal carcinoma cell lines and normal nasopharyngeal mucosal cells.2.Immunohistochemistry detected the correlation between ARID1 A and the clinicopathological characteristics of nasopharyngeal carcinoma.3.CCK-8 detected the effect of ARID1 A knockdown on the proliferation of nasopharyngeal carcinoma CNE1 and HNE1 cells;4.Flow cytometry deteced the effect of ARID1 A knockdown on the cell cycle of nasopharyngeal carcinoma CNE1 and HNE1 cells;5.Tanswell detected the effect of ARID1 A knockdown on the migration and invasion of nasopharyngeal carcinoma CNE1 and HNE1 cells;6.Western blot detected the effect of ARID1 A knockdown on the expression of related proteins in Akt signaling pathway of nasopharyngeal CNE1 and HNE1 cells.Results: 1.IHC,PCR and WB showed that ARID1 A is down regulated in NPC tissues and cells;2.IHC showed that lower ARID1 A expression was associated with histological grade and advanced TNM stage;while no relationship with age and sex;3.CCK-8 showed that ARID1 A knockdown could promote the proliferation of nasopharyngeal carcinoma CNE1 and HNE1 cells;4.Flow cytometry showed that ARID1 A knockdown could promote the apoptosis of nasopharyngeal carcinoma C666-1 cells;5.Transwell assays showed that ARID1 A knockdown could significantly decreased the G0/G1 phase and increased the cell population at S phase of nasopharyngeal carcinoma CNE1 and HNE1 cells;6.WB showed that ARID1 A knockdown in nasopharyngeal carcinoma CNE1 and HNE1 cells promoted the expression of p-Akt,it have no effect on the expression of Akt.Conclusions: 1.ARID1 A was downregulated in NPC tissues;2.ARID1 A was downregulated in NPC cells;3.Lower ARID1 A expression was associated with advanced TNM stage and clinical stages;4.Silencing ARID1 A increased NPC cell proliferation,migration and invasion;5.Down reguated ARID1 A was correlated with the activated Akt pathway in NPC cells and in clinical NPC biopsies.