FOXA2 promotes the proliferation, migration and invasion, and epithelial mesenchymal transition in colon cancer

Abstract

The present study determined the expression and biological functions of FOXA2 gene in colon cancer in tissues, cells and animals. A total of 66 patients with colon cancer were included in the present study. Using The Human Protein Atlas database, expression and distribution of FOXA2 in colon cancer tissues were analyzed. Using immunohistochemistry, the expression and distribution of FOXA2 in colon cancer cells were studied. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine the expression of FOXA2 mRNA in colon cancer tissues. Following in vitro transfection with FOXA2 interference sequence (siR-FOXA2), the proliferation, cell cycle, migration and invasion of colon cancer HCT116 and HT29 cells were investigated using Cell Counting Kit-8 assay, flow cytometry, and Transwell assay, respectively. Furthermore, flow cytometry was used to determine apoptosis of HCT116 and HT29 cells. Western blotting was used to determine the expression of epithelial mesenchymal transition (EMT) proteins, E-Cadherin and Vimentin. Laser scanning confocal microscopy was performed to observe the cytoskeleton in HCT116 and HT29 cells. Results indicated tumorigenesis of colon cancer cells in nude mice. In addition, the expression of FOXA2 in colon cancer tissues was elevated and associated with the metastasis and clinical staging of colon cancer. Notably, inhibition of FOXA2 reduced the proliferation of colon cancer cells in vitro and reduced expression of FOXA2 was able to decrease the migration and invasion abilities of colon cancer cells. Furthermore, FOXA2 promoted EMT, inhibited apoptosis and enhanced the invasion ability of colon cancer cells. Decreased expression of FOXA2 inhibited tumorigenesis of colon cancer cells in nude mice. To conclude, the present study demonstrated that the expression of FOXA2 in colon cancer tissues was elevated and associated with the metastasis and clinical staging of colon cancer. As an oncogene, FOXA2 may promote the proliferation, migration and invasion and EMT in colon cancer.

LINC00261 Is an Epigenetically Regulated Tumor Suppressor Essential for Activation of the DNA Damage Response

“…Many studies implicate FOXA2 as a tumor suppressor, equating this transcription factor as a differentiation signal that antagonizes cancer to help maintain the normal state. However, the actual mechanism by which FOXA2 exerts a tumor suppressing role is unknown, and there are also a few studies that demonstrate a pro-oncogenic role for FOXA2 in other epithelial cancers (42). Studies have evaluated the binding site affinity for FOXA2 (vs. the homolog FOXA1) and seen enrichment in lipid metabolism genes, none of which were implicated in its effect on carcinogenesis (43).…”

LncRNA FTX activates FOXA2 expression to inhibit non–small‐cell lung cancer proliferation and metastasis

“…Meanwhile, Shandy Shahabi et al found that hypermethylation in FOXA2 gene promoter region suppressed FOXA2 expression in LUAD, and ectopic expression of FOXA2 in LUAD cells inhibited cell migration and proliferation through activating LINC00261 expression . However, FOXA2 was reported to promote proliferation and migration in colon cancer . Although there are conflicting data of the function of FOXA2 in cancer progression, in the present study, our results suggested that FOXA2 silencing promoted cell proliferation and migration in lung cancer cells.…”

Development and Verification of an Immune-Related Gene Pairs Prognostic Signature in Ovarian Cancer

“…It has also been reported to be involved in the occurrence and development of gastric cancer (41) and hepatocellular cancer (42). In addition, the expression of forkhead box A2 (FOXA2) in colon cancer tissues is upregulated and related to the metabolism and clinical stages (43). Moreover, FOXA2 is capable of facilitating EMT, inhibiting apoptosis and enhancing colon cancer cell invasion ability.…”