Effect Of Sox13 On Malignant Phenotype Of Colorectal Cancer And Its Mechanisms

Colorectal cancer is one of the common malignant tumors of the digestive system.Global cancer statistics shows that the incidence and mortality of colorectal cancer in cancer are third and second.Respectively,Colorectal cancer seriously threatens human health.Elucidating the molecular mechanism of colorectal cancer occurrence and development,and finding effective prognostic markers and intervention targets are of great significance to improve the long-term survival rate of cancer patients.The Sox family is a class of transcription factor-encoding genes with highly conserved HMG-box sequences,which are widely involved in the development and maturation of embryos and determining the fate and differentiation of cells.Studies have shown that members of the Sox family play an important role in the development and metastasis of tumors.However,there are few studies on Sox 13 in tumors.In this research,we investigated the effects and the molecular mechanisms of Sox13 on colorectal cancer cells proliferation,apoptosis,invasion and metastasis through in vivo animal experiments and in vitro cell experiments.First,the analysis of Sox13 expression in human colorectal cancer tissues revealed that Sox 13 was obviously lower in cancer tissues than adjacent tissues.Sox 13 can inhibit the invasion and migration of colorectal cancer cells in knockdown or overexpression of Sox 13 in colorectal cancer cells.We established a lung metastasis model by tail vein injection in mice to verify that knockdown Sox13 can promote the colonization ability of colorecal cancer cells in mices.The mechanism study showed that Sox13 and E-cadherin were positively correlated at both mRNA and protein levels.We have constructed luciferase reporter plasmids and the sequence deletion and mutation.The luciferase reporter assay showed that Sox 13 was able to activate E-cadherin by transcription.Then ChIP experiments showed that Sox 13 can directly bind to the promoter region of E-cadherin to regulate the expression of E-cadherin and inhibit the proliferation of colorectal cancer cells.In addition,studies have shown that Sox 13 can inhibit the growth and colony-forming ability of colorectal cancer cells.Through cell flow experiments,it was found that the apoptosis rate of HCT-15 tumor cells of overexpressing Sox13 was lower than the control group,and the apoptosis of HCT-116 and HCT-8 tumor cells was reduced after knocking down Sox 13.The expression of BAX and PARP1 decreased and the expression of inhibitory apoptotic proteins(BCL-2,MCL-1)increased.As a newly discovered tumor suppressor gene,Fbxw7 plays an important role in regulating cell growth and differentiation in the human cell cycle.Studies on the molecular mechanism of proliferation and apoptosis found that Sox 13 and Fbxw7 expression were positively correlated at the mRNA level.Sox 13 is capable of transcriptionally activating Fbxw7,and directly binds to the upstream region of the Fbxw7 promoter to up-regulate Fbxw7 expression to inhibit the proliferation of colorectal cancer cells.The mouse subcutaneously transplanted tumor model was used to verify the ability of Sox13 to inhibit tumor cell proliferation in vivo.In summary,the results of the study found that Sox13 expression decreased in colorectal cancer tissues.In vitro experiments confirmed that Sox13 protein played a significant role in inhibiting metastasis and proliferation in colorectal cancer cells.Sox13 inhibits the migration and invasion of colorectal cancer cells through transcriptional activation of E-cadherin.Sox13 positively regulates Fbxw7,which may be related to the effect of Sox13 on the proliferation of colorectal cancer cells,suggesting that Sox13 may be a potential therapeutic target for colorectal cancer.