(2020) Tanshinone I induces cell apoptosis by reactive oxygen species-mediated endoplasmic reticulum stress and by suppressing p53/DRAM-mediated autophagy in human hepatocellular carcinoma,
The aberrant expression of forkhead box P3 (FOXP3) leads to the formation of malignant tumors. FOXP3 expression levels are also elevated in hepatocellular carcinoma (HCC). The aim of the present study was to investigate the effects of FOXP3 silencing on cell proliferation, migration, apoptosis and chemokine/chemokine receptor expression in the MHCC-97H HCC cell line. Three FOXP3 short hairpin (sh)RNA constructs were designed: Sh-FOXP3-1-pGreenPuro, sh-FOXP3-2-pGreenPuro, and sh-FOXP3-3-pGreenPuro. MHCC-97H cells were transfected with shRNA-FOXP3, and the mRNA and protein expression levels of C-X-C motif chemokine (CXC) ligand 12 (CXCL12), CXCL11, CXC receptor 4 (CXCR4) and CXCR7 were measured. Cell Counting Kit-8, terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling and Transwell assays were used to evaluate cell proliferation, apoptosis and migration, respectively. Of the three FOXP3 lentivirus carriers constructed, sh-FOXP3-1 significantly reduced FOXP3 expression levels and was chosen for further experiments. sh-FOXP3-1 inhibited cell proliferation, promoted apoptosis and inhibited cell migration compared with the negative control. The mRNA and protein expression levels of CXCL12, CXCL11, CXCR4 and CXCR7 were decreased significantly in response to FOXP3 silencing. FOXP3 silencing may therefore inhibit cell growth, induce apoptosis and inhibit migration in HCC cells, possibly by impairing the chemokine/chemokine receptor axes.
Background: Previous studies reported that FOXP3 is involved in the regulation of tumor microenvironment and the regulation of tumor local immunity. However, its mechanism has not been fully studied. This study aims to explore the potential relationship between FOXP3 and cancer immunotherapy in 33 human cancers.Method: The gene expression data and clinical characteristics of 33 cancers were retrieved from the Cancer Genome Atlas database. The immunotherapy cohort includes GSE157893, GSE67501, and IMvigor210, which come from a comprehensive gene expression database and are included in previously published studies. Analyze clinical parameters, including patient age, gender, and tumor stage to assess the prognostic value of FOXP3. At the same time, we conducted survival analysis and correlation analysis of tumor microenvironment. The correlation between FOXP3 and immunosuppressive agents and stimulants, as well as major histocompatibility complexes was also analyzed. Potential pathways related to FOXP3 signaling in cancer have also been explored. In addition, the correlation between FOXP3 and two immunotherapy biomarkers (tumor mutation burden and microsatellite instability) was studied. Finally, the immunotherapy response relationship between FOXP3 and the immunotherapy cohort was explored.Results: Among 33 cancer types, FOXP3 expression is different in different clinical groups (gender, age, and tumor stage) in certain cancers, and it also shows potential prognostic value in predicting patient survival. FOXP3 is correlated with immune cell infiltration, immunomodulators and immunotherapy markers. In addition, low FOXP3 expression is significantly associated with certain pathways. However, no significant correlation was observed between FOXP3 and immunotherapy response.Conclusion: This study explored the immunotherapy value of FOXP3 in 33 human cancers, and provided evidence and insights for the application of FOXP3 in tumor immunotherapy. However, considering the bioinformatics methods used in this study, the findings of the study are only preliminary, and more relevant experimental verifications are needed.
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