Depletion of the m6A demethylases FTO and ALKBH5 impairs growth and metastatic capacity through EMT phenotype change in clear cell renal cell carcinoma

被引：0
|
作者：
Hu, Wei [1 ,2 ,3 ]
Klumper, Niklas [1 ]
Schmidt, Doris [1 ]
Ritter, Manuel [1 ]
Ellinger, Jorg [1 ]
Hauser, Stefan [1 ,4 ]
机构：
[1] Univ Hosp Bonn, Dept Urol, Bonn, Germany
[2] Wuhan Univ, Renmin Hosp, Dept Urol, Wuhan, Hubei, Peoples R China
[3] Wuhan Univ, Renmin Hosp, Dept Urol, Jiefang Rd 238, Wuhan 430060, Hubei, Peoples R China
[4] Univ klinikum Bonn, Klinik & Poliklin Urol & Kinderurol, Bonn, Germany
来源：
AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH | 2023年 / 15卷 / 03期
关键词：
m6A-erasers; clear cell renal cell carcinoma (ccRCC); epithelial-mesenchymal transition (EMT); FTO; ALKBH5; DNA METHYLATION ANALYSIS; RNA; EXPRESSION; ERASERS;
D O I：
暂无
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Background: N6-methyladenosine (m6A) is one of the most common RNA modifications in eukaryotes and has effects on RNA structure and stability. Recent studies have shown that m6A methylation is involved in human carcinogenesis. In the present study, we investigated the effects of m6A demethylases FTO and ALKBH5 on renal cell carcinoma (RCC) cell lines. Methods: The epithelial-mesenchymal in vitro knockdowns of FTO and ALKBH5 induced by antisense oligonucleotides (LNA-GapmeR system) were established in RCC cell lines. Their effects on migration and proliferation were investigated subsequently. The influence of FTO and ALKBH5 knockdown on key epithelialmesenchymal transition (EMT) genes was analyzed. Results: Inactivation of FTO and ALKBH5 resulted in decreased proliferation and motility in all cell lines examined (ACHN, Caki-1, 769-P). Vimentin (VIM) was downregulated after the knockdown of FTO and ALKBH5, indicating an EMT switch. Conclusions: Knockdown of the m6A erasers FTO and ALKBH5 inhibits the malignant potential in the cell cultures studied by means of an EMT switch.
引用
收藏
页码：1744 / +
页数：14
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