Background: IL-37 is a newly anti-inflammatory cytokine whose function is largely unknown in cancer.Our preliminary experiment found IL-37 could inhibit the invasion of human cervical cancer (CC) cells and influence the expression of RUNX family whose function was also unclear in CC. The present study aims to further investigate the effects of IL-37 on cell invasion and runt related transcription factor 2 (RUNX2) expression in CC cell lines.Methods: Firstly, plasmid overexpressing IL-37 or RUNX2 was transfected into Siha and C33A cells by Hilymax. Then, the effects of IL-37 on the mRNA expression of RUNX1, RUNX2 and RUNX3 gene were detected by quantitative real-time polymerase chain reaction. Protein expression was measured by Western blot and the grayscale scanning analysis. Finally, the effects of IL-37 or RUNX2 on cell invasion were tested by transwell assay.Results: IL-37 inhibited the mRNA expression of RUNX1 and RUNX2, and increased that of RUNX3 in CC cells. Among the three RUNX genes, RUNX2 showed the most significant change in mRNA expression (decreased by78.5% in Siha cells and by 61.5% in C33A cells) and thus was chosen for the following study.Overexpressed IL-37 inhibited cell invasion by 36.23% in Siha cells (P<0.05) and 26.21% in C33A cells (P<0.01). Overexpression of RUNX2 promoted cell invasion. Up-regulation of IL-37 suppressed markedly the mRNA and protein expression of RUNX2. Furthermore, overexpressed RUNX2 partially restored the inhibited cell invasion by IL-37 to 86.62% in Siha cells (P<0.01) and 87.08% in C33A cells (P<0.01).Conclusions: IL-37 can significantly inhibit the cell invasion of Siha and C33A cells, which involves the suppression of RUNX2.
The role of IL-37 in cancer is currently largely unknown. The present study aimed to investigate IL-37 expression in hepatocellular carcinoma (HCC), paracancerous tissues (PT) and liver cancer cell lines, and their associations between IL-37 and NF-κB. A total of 65 HCC and 65 PT tissues were collected. The expression of IL-37 and NF-κB in tissues was detected by immunohistochemistry (IHC) and the data was analyzed using SPSS software. In the in vitro studies, IL-37 gene was transfected into HepG2 and MHCC97H cell lines with Lipofectamine 3000, and the protein regulation of NF-κB by IL-37 was verified by immunofluorescence (IF) and western blotting. In HCC, the positive expression rates of IL-37 and NF-kB were 21.5 and 95.4%, respectively. In PT, strong positive staining of IL-37and weak positive staining of NF-κB were observed. The normal expression levels of IL-37 and NF-κB, the increased IL-37 and decreased NF-κB induced by IL-37 gene transfection were observed through IF in cell lines. In terms of clinical significance, the difference in IL-37 expression between HCC and PT was statistically significant (χ 2 =55.05; P<0.001). IL-37 expression in HCC but not PT was negatively associated with serum AFP (χ 2 =6.522; P=0.039). IL-37 expression in PT was associated with sex (χ 2 =13.12; P=0.003) and tumor size (χ 2 =7.996; P=0.045). NF-κB expression in PT was associated with age, sex and BCLC stage. Notably, there was a negative correlation between IL-37 and NF-κB in HCC (r=-0.277; P=0.029) but not in PT (P>0.05). IL-37 overexpression downregulated the NF-κB protein by 56.50% in HepG2 cells (P<0.05) and 30.52% in MHCC97H cells (P<0.05). In conclusion, the expression of IL-37 in HCC and PT was specifically associated with serum AFP and tumor size, respectively. IL-37 expression was negatively correlated with NF-κB protein expression in HCC tissues and liver cancer cell lines.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.