CircNTNG1 inhibits renal cell carcinoma progression via HOXA5-mediated epigenetic silencing of Slug

作者：Yanping Liang, Junjie Cen, Yong Huang, Yong Fang, Yunfei Wang, Guannan Shu, Yihui Pan, Kangbo Huang, Jiaqi Dong, Mi Zhou, Yi Xu, Junhang Luo, Min Liu, Jiaxing Zhang · 发表于：Molecular Cancer · 年份：2022 · DOI：10.1186/s12943-022-01694-7 · 被引用次数：29 · 研究领域：Circular RNAs in diseases、MicroRNA in disease regulation、Connective Tissue Growth Factor Research

BACKGROUND: Recent studies have identified that circular RNAs (circRNAs) have an important role in cancer via their well-recognized sponge effect on miRNAs, which regulates a large variety of cancer-related genes. However, only a few circRNAs have been well-studied in renal cell carcinoma (RCC) and their regulatory function remains largely elusive. METHODS: Bioinformatics approaches were used to characterize the differentially expressed circRNAs in our own circRNA-sequencing dataset, as well as two public circRNA microarray datasets. CircNTNG1 (hsa_circ_0002286) was identified as a potential tumor-suppressing circRNA. Transwell assay and CCK-8 assay were used to assess phenotypic changes. RNA pull-down, luciferase reporter assays and FISH experiment were used to confirm the interactions among circNTNG1, miR-19b-3p, and HOXA5 mRNA. GSEA was performed to explore the downstream pathway regulated by HOXA5. Immunoblotting, chromatin immunoprecipitation, and methylated DNA immunoprecipitation were used to study the mechanism of HOXA5. RESULTS: In all three circRNA datasets, circNTNG1, which was frequently deleted in RCC, showed significantly low expression in the tumor group. The basic properties of circNTNG1 were characterized, and phenotype studies also demonstrated the inhibitory effect of circNTNG1 on RCC cell aggressiveness. Clinically, circNTNG1 expression was associated with RCC stage and Fuhrman grade, and it also served as an independent predictive factor for both OS and R...