SOX7 Target Genes And Their Contribution To Its Tumor Suppressive Function

SOX7 belongs to the SOXF subfamily,which can participate in the regulation of various biological processes in embryonic development,and plays a tumor suppressive role in various cancers as a tumor suppresser.Previous studies have indicated that SOX7 can regulate the expression of multiple genes,but none of them was carried out in cancer-relevant context.In this study,we used microarray chips to determine alterations of gene expression in MDA-MB-231 cells with DOX-induced SOX7 expression and discovered multiple potential target genes regulated by SOX7.When combinatorially analyzing a gene array dataset from a breast cancer cohort,we identified four SOX7-related target genes;SPRY1 and SLIT2 are potential activated by SOX7,while TRIB3 and MTHFD2 are likely repressed by SOX7.Thus,we determined whether these genes played key roles in SOX7-mediated tumor suppression.The obtained results include:1.Using luciferase reporter vector and real-time quantitative PCR technology,we demonstrated that SOX7 can regulate the expression of four target genes of SPRY1,SLIT2,TRIB3 and MTHFD2.The results of chromatin immunoprecipitation assays have confirmed the binding of SOX7 to the promoters of these four genes.2.In MDA-MB-231 cells with DOX-inducible SOX7,we individually inverted expression of these four target genes of SOX7 by knocking down SOX7-activated SPRYI and SLIT2,or ectopically expressing SOX7-repressed TRIB3 and MTHFD2,and studied the effects on cell proliferation.We observed that reversing the expression of these gene,especially MTHFD2,could partially rescue the defects caused by induced SOX7 expression in breast cancer cells,suggesting that these four genes differentially contribute to SOX7-mediated tumor suppression.