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

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. K E Y W O R D Sclear cell renal cell carcinoma, progression, runt-related transcription factor 2, stearyl CoA desaturase 1, Wnt/β-catenin Funding informationNo particular grant that belonged to funding agencies in public, commercial, or nonprofit fields was given to such a study.

Role of RUNX2 in breast cancer development and drug resistance (Review)

“…Meanwhile, the dysregulation and alteration of RUNX2 expression or activity may result in arteriosclerosis, skeletal dysplasia (e.g., cleidocranial dysplasia) and tumorigenesis (4,(12)(13)(14). For instance, RUNX2 is involved in the progression of various tumor types, such as osteosarcoma, renal cell carcinoma, gastric cancer and breast cancer (15)(16)(17)(18)(19)(20). For instance, a recent study by our group reported the facilitating effect of RUNX2 during aggressiveness and chemoresistance of TNBC cells via activating MMP1, which was significantly associated with poor prognosis (21).…”

Integrated bioinformatics and network pharmacology to identify the therapeutic target and molecular mechanisms of Scutellaria barbata plus Hedyotis diffusa herb pair on esophageal squamous cell carcinoma

“…Several studies have also con rmed that CAV1 expression is closely related to ESCC, and it could be a powerful prognostic marker for patients with ESCC [67][68][69] . RUNX2 is related to a variety of tumors, particularly tumor invasion and metastasis [70] . It has been reported that RUNX2 was highly expressed in esophageal carcinoma tissues and cells, while knockdown of RUNX2 markedly suppressed tumor formation in vivo [71] .…”

RUNX2 and Cancer

“…In ccRCC, RUNX2 triggered cancer cell proliferation via SCD1-dependent Wnt/β-catenin pathway activation. RUNX2 downregulation inhibited cancer cell proliferation [ 11 ]. In another study of ccRCC, the biological function of RUNX2 was to increase focus formation, Ki67-positive staining, and tumor volume in a xenograft model.…”

“…The role of RUNX2 in the clear cell subtype of RCC (ccRCC) cell migration was addressed. RUNX2 overexpression led to an increase in cell migration ability, and this elevated migration was partially reduced by the downregulation of SCD1 [ 11 ]. Activation of Zic2/Runx2/NOLC1 signaling promoted ccRCC cell migration and lung metastasis in vivo [ 12 ].…”