RUNX2 interacts with SCD1 and activates Wnt/β‐catenin signaling pathway to promote the progression of clear cell renal cell carcinoma

Abstract

Abstract Background Previous studies have demonstrated that Runt‐associated transcription factor 2 (RUNX2) serves as the main transcription factor for osteoblast differentiation and chondrocyte maturation. RUNX2 is related to a variety of tumors, particularly tumor invasion and metastasis, while the expression and molecular mechanisms of RUNX2 in clear cell renal cell carcinoma (ccRCC) keep to be determined. Stearyl CoA desaturase 1 (SCD1), an endoplasmic reticulum fatty acid desaturase, transfers saturated fatty acids to monounsaturated fatty acids, is expressed highly in numerous malignancies. Methods The Cancer Genome Atlas (TCGA) datebase and Western blot was used to analyzed the mRNA and protein levels of the target gene in ccRCC tissues and adjacent tissues. The proliferation ability of ccRCC cells was tested by colony forming and EdU assay. The migration ability of cells was detected by transwell assay. Immunoprecipitation was utilized to detect protein–protein interaction. Cycloheximide chase assay was used to measure the half‐life of SCD1 protein. Results In this study, the expressions of RUNX2 and SCD1 are increased in ccRCC tissues as well as ccRCC cell lines. Both RUNX2 and SCD1 could promote proliferation and migration in ccRCC cells. Furthermore, RUNX2 could physically interact with SCD1. In addition, the functional degradation and the inactivation of Wnt/β‐catenin signaling pathway triggered by the downregulation of RUNX2 could be partly offset by the overexpression of SCD1. Conclusion The findings indicate that the RUNX2/SCD1 axis may act as a potential therapeutic target via the Wnt/β‐catenin signaling pathway of ccRCC.

Keywords

• clear cell renal cell carcinoma
• progression
• runt‐related transcription factor 2
• stearyl CoA desaturase 1
• Wnt/β‐catenin