J Cancer 2022; 13(4):1181-1192. doi:10.7150/jca.62433 This issue
Department of integration of traditional Chinese and Western Medicine and anorectum, the First Affiliated Hospital of Nanchang University, Nanchang, China
Background: Colorectal cancer (CRC) is the third most common cancer worldwide. Several studies have suggested that FOXP2 functions as a tumour suppressor. However, to date, it remains unclear how FOXP2 influences CRC occurrence.
Methods: We took advantage of CRC tissue samples and compared the expression of FOXP2 via immunohistochemistry assays. We elucidated the underlying function of FOXP2 in CRC cells by constructing a cell model with FOXP2 depletion. Co-IP experiments and immunofluorescence (IF) assays were conducted, and the results demonstrated that FOXP2 can promote the activation of caspase-1 to enhance cell pyroptosis.
Results: We used tissue RNA sequencing analysis in a colitis-associated cancer mouse model, and found that FOXP2 was downregulated in colitis and tumour tissues. We also found that CRC patients with low FOXP2 expression had poorer survival. Cell viability assays and electron microscopic examination showed that depletion of FOXP2 could enhance cell growth and inhibit cell pyroptosis. At the same time, knocking down FOXP2 expression was able to promote the protein expression of PCNA and cyclin D1 and downregulate the expression of the caspase family of proteins and GSDMD, which are markers of pyroptosis. A series of co-IP and IF assays revealed that FOXP2 interacts with caspase-1 and promotes its expression.
Conclusion: Our findings reveal a key role for FOXP2 in CRC cell pyroptosis and provide a mechanism explaining how FOXP2 promotes cell pyroptosis.
Keywords: colorectal cancer, FOXP2, caspase-1, cell pyroptosis