WITHDRAWN: Evaluation of PAX8 Expression Promotes the Proliferation of Stomach Cancer cells

Abstract

Background: PAX8 was identified as a mitosis-related regulator involved in the pathogenesis of human tumors and an indicator of the prognosis for patients. However, PAX8 function on proliferation in stomach cancer have not been studied. Aim: This study was aimed to explore the expression pattern of PAX8 in stomach cancer, and investigate the effect of PAX8 on the proliferation of stomach cancer cells. Methods: PAX8 expression pattern in stomach cancer was investigated in the “TCGA” database and compared in cancer and adjacent tissues of 36 clinical samples, in which the co-expression of SOX13 and PAX8 was confirmed by qRT-PCR. Based on the clinical record and IHC staining results, the survival curve was also mapped. Western blotting and qRT-PCR was used to analyze the effect of SOX13 on PAX8 expression in AGS and MGC803 cells, and the downstream effector Aurora B and Cyclin B1 expression. ChIP and luciferase assay were performed to explore SOX13 locate on the promoter of PAX8. Furthermore, CCK8, clone formation, EdU incorporation assay, and flow cytometry were used to detect the proliferative ability of AGS and MGC803 cell lines stably silenced PAX8. Results: PAX8 and SOX13 were identified to be synchronously upregulated in primary stomach cancer tissues and the stomach cancer TCGA datasets, and stomach cancer patients of combined high PAX8 and SOX13 expression showed worse prognosis. Furthermore, SOX13 can mediate PAX8 and its targeted genes expression, including Aurora B and Cyclin B1, in AGS and MGC803 cell lines. Flow cytometry and EdU incorporation assays showed that silencing PAX8 can block the cell cycle of stomach cancer cell in G1 phase and SOX13 expression can rescue the arrested proliferative process induced by PAX8 silenced in CCK8 and colony formation assays. Conclusion: -SOX13 participated in the elevated expression of PAX8, which promote the proliferation of stomach cancer cells, and both SOX13 and PAX8 play an oncogene role in stomach cancer.