METTL3 and IGF2BP1-Mediated m6A Modification of ZHX2 Promotes Tumor Property of Renal Cell Carcinoma

作者：Bangming Xiao, Yalan Li, Yong Yang, Congbo Chen, Shide Gong, Hao Li, Qisheng Yao, Wang Li · 发表于：Kidney & Blood Pressure Research · 年份：2024 · DOI：10.1159/000540483 · 被引用次数：12 · 研究领域：RNA modifications and cancer、Cancer-related gene regulation、Ubiquitin and proteasome pathways

INTRODUCTION: Renal cell carcinoma (RCC) is a common type of kidney cancer with limited treatment options and a high mortality rate. Therefore, it is essential to understand the role and mechanism of key genes in RCC development and progression. This study aimed to analyze the role of zinc fingers and homeoboxes 2 (ZHX2) in RCC and the underlying mechanism. METHODS: RNA expression was analyzed by quantitative real-time polymerase chain reaction, while protein expression was analyzed by Western blotting assay and immunohistochemistry assay. Cell viability was evaluated using CCK-8 assay, and cell proliferation was assessed by EdU assay. The rate of cell apoptosis was quantified by flow cytometry. Transwell assays were conducted to analyze cell migration and invasion. The sphere formation assay was performed to assess the formation of microspheres. Additionally, m6A RNA immunoprecipitation assay and RNA immunoprecipitation assay were utilized to investigate the relationship between ZHX2 and two proteins, methyltransferase like 3 (METTL3) and insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1). The stability of ZHX2 mRNA was analyzed through the Actinomycin D assay. Furthermore, a xenograft mouse model assay was conducted to analyze the effect of ZHX2 overexpression and METTL3 silencing on RCC cell tumor properties in vivo. RESULTS: ZHX2 expression was upregulated in both RCC tissues and cells when compared with healthy renal tissues and human renal cortex proximal con...