RNA N6-methyladenosine modification mediates downregulation of NR4A1 to facilitate malignancy of cervical cancer
Tao Yu, Fuxia Wu, Yan Jia, Xue Zhang, Xiaozhen Qi, Zeyuan Jin, Tongxin Hao, Jianing Zhao, Ziyu Liu, Chaokun Wang, Minmin Niu, Qin Yue, Min Li, Yankun Liu
Abstract
Abstract Background N 6 -methyladenosine is the most abundant eukaryotic mRNA modification and alters a wide range of cellular processes in cancer. Therefore, defining the molecular details are critical for understanding the regulatory mechanism of m 6 A modification. Results We found that METTL3, a core m 6 A methyltransferase component, is upregulated and functions as an oncogene in cervical cancer. Mechanistically, METTL3 induces the degradation of m 6 A-modified transcripts of NR4A1 though YTHDF2-DDX6 pathway. In addition, NR4A1 overexpression attenuates the malignant progression through recruiting the LSD1/HDAC1/CoREST transcriptional repression complex to AKT1 promoter. Conclusions Our findings reveal that m 6 A regulates cervical cancer cellular progression through manipulating NR4A1 pathway.