Department of Urology, The First Hospital of China Medical University, Shenyang, Liaoning, P. R. China.
Department of Urology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, P. R. China.
Cancer Med. 2023 Mar;12(5):5764-5780. doi: 10.1002/cam4.5326. Epub 2022 Oct 6.
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.
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.
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.
The findings indicate that the RUNX2/SCD1 axis may act as a potential therapeutic target via the Wnt/β-catenin signaling pathway of ccRCC.
先前的研究表明， runt 相关转录因子 2（RUNX2）是成骨细胞分化和软骨细胞成熟的主要转录因子。RUNX2 与多种肿瘤有关，尤其是肿瘤的侵袭和转移，而 RUNX2 在透明细胞肾细胞癌（ccRCC）中的表达和分子机制仍有待确定。硬脂酰辅酶 A 去饱和酶 1（SCD1），一种内质网脂肪酸去饱和酶，将饱和脂肪酸转移到单不饱和脂肪酸，在许多恶性肿瘤中表达水平较高。
使用癌症基因组图谱（TCGA）数据库和 Western blot 分析 ccRCC 组织和相邻组织中靶基因的 mRNA 和蛋白水平。通过集落形成和 EdU 测定试验检测 ccRCC 细胞的增殖能力。通过 Transwell 测定试验检测细胞的迁移能力。利用免疫沉淀检测蛋白-蛋白相互作用。利用环己酰亚胺追踪试验测量 SCD1 蛋白的半衰期。
在本研究中，RUNX2 和 SCD1 的表达在 ccRCC 组织和 ccRCC 细胞系中均增加。RUNX2 和 SCD1 均可促进 ccRCC 细胞的增殖和迁移。此外，RUNX2 可与 SCD1 发生物理相互作用。此外，下调 RUNX2 触发的 Wnt/β-catenin 信号通路的功能降解和失活可以部分被 SCD1 的过表达所抵消。
这些发现表明，RUNX2/SCD1 轴可能通过 ccRCC 的 Wnt/β-catenin 信号通路作为潜在的治疗靶点。
