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

被引：13

作者：

Yu, Tao ^{[1
]}

Wu, Fuxia ^{[1
]}

Jia, Yan ^{[1
]}

Zhang, Xue ^{[1
]}

Qi, Xiaozhen ^{[1
]}

Jin, Zeyuan ^{[1
]}

Hao, Tongxin ^{[1
]}

Zhao, Jianing ^{[1
]}

Liu, Ziyu ^{[1
]}

Wang, Chaokun ^{[3
]}

Niu, Minmin ^{[1
]}

Yue, Qin ^{[1
]}

Li, Min ^{[1
]}

Liu, Yankun ^{[2
]}

机构：

[1] Tianjin Med Univ, Sch Basic Med Sci, Dept Pathogen Biol, Tianjin 300070, Peoples R China

[2] Tangshan Peoples Hosp, Dept Mol Diag, Tangshan 063001, Peoples R China

[3] Tianjin Med Univ, Sch Basic Med Sci, Dept Integrat Chinese & Western Med, Tianjin 300070, Peoples R China

来源：

CELL AND BIOSCIENCE | 2022年 / 12卷 / 01期

关键词：

RNA N-6-methyladenosine; METTL3; YTHDF2; Cervical cancer; AKT1; G-QUADRUPLEXES; TRANSLATION; METHYLATION; REVEALS; METTL3; ENRICHMENT; PROMOTER; SP1;

D O I：

10.1186/s13578-022-00937-w

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：18

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