RNA N6-methyladenosine modification mediates downregulation of NR4A1 to facilitate malignancy of cervical cancer

Author:

Yu TaoORCID,Wu Fuxia,Jia Yan,Zhang Xue,Qi Xiaozhen,Jin Zeyuan,Hao Tongxin,Zhao Jianing,Liu Ziyu,Wang Chaokun,Niu Minmin,Yue Qin,Li Min,Liu Yankun

Abstract

Abstract Background N6-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 m6A modification. Results We found that METTL3, a core m6A methyltransferase component, is upregulated and functions as an oncogene in cervical cancer. Mechanistically, METTL3 induces the degradation of m6A-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 m6A regulates cervical cancer cellular progression through manipulating NR4A1 pathway.

Funder

Natural Science Foundation of Tianjin City

Publisher

Springer Science and Business Media LLC

Subject

General Biochemistry, Genetics and Molecular Biology

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