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Role of IL-22/IL-22RA1 pathway in the malignant progression of oral squamous carcinoma and its mechanism
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Abstract:
Objective: To investigate the role of IL-22/IL-22RA1 (IL-22 receptor A1) pathway in the malignant progression of oral squamous cell carcinoma (OSCC) and the underlying mechanisms. Methods: The expression levels of IL-22RA1 in OSCC tissues and paired para-cancerous tissues were analyzed using the GEO database and immunohistochemistry. The association between IL-22RA1 expression and the clinicopathological characteristics of OSCC patients was detected and analyzed by tissue microarray immunohistochemistry. The relationship between IL-22RA1 expression and the prognosis of OSCC patients was analyzed using the EBI ArrayExpress database. The expression of IL-22 and IL-22RA1 in OSCC tissues was examined by immunofluorescence, and their association was also analyzed. IL-22RA1 expression was knocked down in OSCC WSU-HN4 and CAL27 cells by RNA interference technology, and the efficiency was verified using qPCR. The effects of IL-22 on the colonogenesis and migration of OSCC cells in the negative control (siNC) group and IL-22RA1 knock-down (siIL-22RA1) group were determined by plate cloning and transwell assays, respectively. The effects of IL-22 on the expression of IL-22RA1 and the phosphorylation level of STAT1, STAT3 and ERK1/2 in OSCC cells were detected using the WB assay. Results: The mRNA expression of IL-22RA1 in OSCC tissues was significantly higher than that in para-cancerous tissues (P<0.05). The expression of IL-22RA1 was associated with tumor size (P<0.05), lymph node metastasis (P<0.01), and poor prognosis (P<0.05) of OSCC patients. There was no significant correlation between the expression levels of IL-22 and IL-22RA1 in OSCC tissues, and IL-22 did not affect on the expression level of IL-22RA1 in OSCC cells (all P>0.05). IL-22 significantly enhanced the colony formation and migration abilities (all P<0.01) of OSCC cells, and activated STAT1, STAT3 and ERK1/2 signals in OSCC cells. After knocking down IL-22RA1 in OSCC cells, IL-22 could not exert the above effects. Conclusion: IL-22/IL-22RA1 can promote the growth and metastasis of OSCC by regulating cell proliferation and migration, and the downstream mechanism may be the activation of ERK1/2-STAT1/3 signaling pathway.
Keywords:
IL-22 ; IL-22RA1 ; oral squamous cell carcinoma (OSCC) ; WSU-HN4 cell ; CAL27 cell ; proliferation ; migration
