The transcriptional regulation of SOX2 on FOXA1 gene and its application in diagnosis of human breast and lung cancers.

Abstract

Recent study demonstrated the important contribution of SOX2 to tumorigenesis and metastasis properties of various types of cancers and strongly supported the concept that SOX2 can be used as an effective marker for diagnosis and predicting prognosis of cancer patients. However, our previous RNA-Seq results from human lung cancer cell line A549 showed that some oncogenes, including FOXA1 are negatively regulated by SOX2. To further verify the transcriptional regulation effect of SOX2 on FOXA1 and elucidate its application in the diagnosis of human lung and breast cancer, we performed real-time RT-PCR and Western blotting to test the regulation effect of SOX2 on the expression of FOXA1 gene. OncoPrint analysis was used to reveal the alteration of SOX2 and FOXA1 genes in breast invasive carcinoma cases and lung squamous cell carcinoma cases from the Cancer Genome Atlas (TCGA) data portal. Immunohistochemistry staining was performed to test the expression of SOX2 and FOXA1 in human breast and lung carcinoma. The results showed that there is an inhibitory effect of SOX2 on the expression of FOXA1 gene. In addition, these two genes are altered in 5.8% of 484 breast invasive carcinoma cases and 46.4% of 179 lung squamous cell carcinoma cases from the Cancer Genome Atlas (TCGA) data portal, which showed an increased percentage of carcinoma cases when compared with single gene alteration. Immunohistochemistry staining of SOX2 and FOXA1 in human breast and lung carcinoma further revealed the mutual complementary effect of these two proteins in the diagnosis of carcinoma. Our study revealed SOX2 as a negative upstream regulator for FOXA1 gene and demonstrated SOX2 and FOXA1 as effective dual markers in improving the diagnosis efficiency for human lung and breast tumor.