Effect Of SOX9 On Biological Function Of Non-Small Cell Lung Cancer Cells

Objective:The purpose of this study is to explore the effects of SOX9 on the biological functions of non-small cell lung cancer cells and preliminarily explore its possible regulatory mechanism,in order to find new markers and therapeutic targets for non-small cell lung cancer.Methods:Construction of SOX9 knockdown cells by transfection of human lung cancer A549 cell line with lentivirus.The plate cloning,Transwell experiment and sphericity test were used to analyze the effects of down-regulation of SOX9 on the proliferation and migration of A549 cells.At the same time,the expression levels of dry markers SOX2,Nanog,OCT4,SALL4 and interstitial marker N-cadherin in SOX9-knocked A549 cells were detected by q RT-PCR and Western-blot.The differentially expressed genes after SOX9 knockdown were analyzed by transcriptome sequencing and the related signaling pathways were enriched to explore the possible related mechanism of SOX9 in regulating the migration,proliferation of lung cancer cells and the characteristics of stem cells.Results:Compared with the control group,the migration and invasion cell number(P < 0.01),clone cell mass number(P < 0.01)and tumor stem cell ball number of A549 cells in SOX9 knockout group were all decreased(P < 0.01).At the same time,SOX9 knockdown inhibited the expression of dryness index SOX2,Nanog,OCT4,SALL4 and epithelial-mesenchymal transition related index N-cadherin(P <0.05).A total of 364 DEGs were screened by comparing SOX9 group with control group.GO analysis showed that differentially expressed genes involved in biological processes such as transforming growth factor β binding,cholesterol synthesis and negative regulation of RNA polymerase on pri-mi RNA transcription.KEGG results showed that related signaling pathways included IL-17 signaling pathway,PPAR pathway,intercellular adhesion molecule and so on.Conclusion:1.Down-regulation of SOX9 inhibits the proliferation,migration and invasion of A549 cells,and SOX9 may promote the occurrence and development of non-small cell lung cancer as an oncogene.2.SOX9 may regulate the stem cell characteristics and EMT process of lung cancer cells,promote the stem cell characteristics of lung cancer cells and inhibit their differentiation characteristics.3.SOX9 participate in the biological regulation of lung cancer stem cells through IL-17 and PPAR signaling pathway.4.SOX9 may become a molecular marker for diagnosis and treatment of lung cancer and a new target for precise treatment.