异位表达
生物
基因敲除
表型
基因
细胞培养
RNA干扰
癌基因
小发夹RNA
基因表达
癌症研究
细胞生物学
细胞周期
遗传学
核糖核酸
作者
Jing Wang,Zhi-Ya Zhang,Jie Jiang,Li Tang,Xiaoyan Wang,Zhen Wang,Xue-Lian Yang,Xinlin Yu,Chenchen Huang,Feng Chen,Shujuan Ye,Haisu Wan
标识
DOI:10.1016/j.bbrc.2022.07.035
摘要
KDM2A is a histone demethylase, which primarily catalyzes the demethylation of H3K36me2. Abnormal expression of KDM2A is observed in many types of cancers; however, the molecular events connected to KDM2A expression remain unclear. We report that KDM2A performs an oncogenic function in esophageal squamous cell carcinoma (ESCC) and is robustly expressed in ESCC cells. ShRNA-mediated knockdown of KDM2A resulted in a significant inhibition of the malignant phenotype of ESCC cell lines, whereas ectopic expression of KDM2A showed the opposite effect. We also analyzed the function of KDM2A using a CRISPR-CAS9 depletion system and subsequent rescue experiment, which also indicated a cancerous role of KDM2A. Interestingly, analysis of the gene expression network controlled by KDM2A using RNA-seq revealed an unexpected feature: KDM2A could induce expression of a set of well-documented oncogenic genes, including IL6 and LAT2, while simultaneously suppressing another set of oncogenes, including MAT2A and HMGCS1. Targeted inhibition of the upregulated oncogene in the KDM2A-depleted cells led to a synergistic suppressive effect on the malignant phenotype of ESCC cells. Our results revealed the dual role of KDM2A in ESCC cells, which may have therapeutic implications.
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