DNMT1 facilitates growth of breast cancer by inducing MEG3 hyper-methylation

Cancer Cell International

Chen Fan¹  Xiaofeng Lu²  Fan Wang²  Lin Lv²  Mingzheng Wang²  Miaomiao Jin²  Shuguang Li²  Xiaotao Zhu² 

[1] Department of Breast Surgery, Women and Children Branch of Jinhua Municipal Central Hospital, 321000, Jinhua, China;Department of Thyroid Breast Surgery, Jinhua Municipal Central Hospital, No. 365 East Renmin Road, 321000, Jinhua, Zhejiang, China;

关键词: DNMT1;    MEG3;    Methylation;    Breast cancer;    Growth;   

DOI  :  10.1186/s12935-022-02463-8

来源: Springer

【 摘 要 】

BackgroundTo understand the effect of DNMT1-mediated MEG3 promoter methylation on breast cancer progression.MethodsExpression of DNMT1, MEG3 and miR-494-3p was assayed by qRT-PCR and western blot. Methylation-specific PCR was used to examine MEG3 promoter methylation level. ChIP, RNA binding protein immunoprecipitation assay and dual-luciferase reporter gene assay were applied to verify interaction between DNMT1 and MEG3, miR-494-3p and MEG3 and OTUD4. CCK-8, wound healing and Transwell assays were used to detect biological functions of breast cancer cells. Tumor growth was observed by tumor xenograft model.ResultsDNMT1 and miR-494-3p were highly expressed while MEG3 and OTUD4 were lowly expressed in breast cancer cells. Knockdown of DNMT1 inhibited progression of breast cancer cells by enhance MEG3 expression through demethylation. MEG3 could downregulate miR-494-3p expression, and OTUD4 was a target of miR-494-3p. Upregulation of MEG3 and downregulation of miR-494-3p both inhibited malignant behavior of cells in vitro. In addition, high MEG3 expression restrained growth of breast cancer in vivo.ConclusionBriefly, our results demonstrated that, DNMT1 induced methylation of MEG3 promoter, and played a key role in breast cancer growth throughmiR-494-3p/OTUD4 axis. These findings provide new insights into molecular therapeutic targets for breast cancer.

【 授权许可】

CC BY