Demethylase FTO inhibits the development of prostate cancer by upregulating EGR2 expression in an m6A manner

Turkish Journal of Biology

article

WANG, ZHENYU¹  SUN, HUAMİN³  ZHU, HUA²  GU, DONGHUA²  CHEN, XİNFENG²  PAN, YONGSHENG²  ZHENG, BİNG²  YANG, DONGRONG¹ 

[1] Department of Urology, The Second Affiliated Hospital of Soochow University;Department of Urology, The Second Affiliated Hospital of Nantong University;Department of Food Safety and School Health, Nantong Center for Disease Control and Prevention

关键词: Prostate cancer;    FTO;    demethylase;    EGR2;   

DOI  :  10.55730/1300-0152.2629

学科分类：生物科学（综合）

来源: Scientific and Technical Research Council of Turkey - TUBITAK

【 摘 要 】

Fat mass and obesity-associated protein (FTO) is a demethylase and plays a vital role in various cancers. However, the regulation mechanism of FTO in prostate cancer (PCa) remains unclear. This study aimed to elucidate the mechanism of FTO in PCa. The function and mechanism of FTO-mediated in PCa were determined by gain-of-function assays and RNA-seq. We found that FTO expression in PCa tissues and two PCa cell lines were significantly lower than that in adjacent tissues and normal cell line. PCa cells after overexpression of FTO showed a significant lower in proliferation, migration, and invasion capabilities. RNA-seq displayed that FTO overexpression altered transcriptome landscape in Du145 and PC-3 cells, particularly upregulating EGR2 expression. FTO overexpression induced differential expression genes, including MYLK2, DNA2, CDK, and CDC (6, 7, 20, 25, and 45), which were mainly enriched in adjustment of cell cycle and growth pathways. Furthermore, FTO overexpression significantly reduced the EGR2 methylation level. Arresting the proliferation, migration, and invasion of Du145 cells induced by FTO overexpression was significantly rescued by EGR2 knockdown. FTO overexpression also significantly inhibited tumor growth and promoted EGR2 protein expression. Taken together, FTO suppresses PCa progression by regulating EGR2 methylation. We uncovered a novel regulatory mechanism of FTO in PCa and provide a new potential therapeutic target for PCa.

【 授权许可】

Unknown