IL1R2 promotes tumor progression via JAK2/STAT3 pathway in human clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is known as the most aggressive subtype of genitourinary cancers. The lack of effective therapies has prompted us to further explore the complex network of genes involved in ccRCC tumor progression and metastasis and to seek new biomarkers and therapeutic strategies to improve clinical outcomes. Interleukin-1 receptor type 2 (IL1R2), a decoy receptor of IL-1, is found to be differentially expressed in various tumors types recently. However, the role of IL1R2 in ccRCC has not been documented. Herein, we found that the expression of IL1R2 in ccRCC tissues was significantly increased as the tumor's Furman pathological grade was elevated. Compared to lower IL1R2 expression, ccRCC patients with high IL1R2 expression had a significantly worse OS rate. IL1R2 could serve as an independent prognostic predictor for ccRCC patients. Depletion of IL1R2 could inhibit cell proliferation, migration, invasion, and cell cycle arrest at the G1 phase, while overexpression of IL1R2 could reverse this effect. Moreover, depletion of IL1R2 led to changes and enrichment of several signaling pathways, as shown by RNA sequencing. We subsequently verified that Janus kinase 2 / signal transducer and activator of transcription 3 (JAK2/STAT3) pathway was involved in the IL1R2 mediated regulation of cellular functions of ccRCC cells and these functions were acted by the intracellular domain of IL1R2, not the extracellular domain. Our findings suggested that IL1R2 could serve as a potential therapeutic target for ccRCC progression and metastasis via its regulation of the JAK2/STAT3 signaling pathway.