MicroRNA-143 is downregulated in breast cancer and regulates DNA methyltransferases 3A in breast cancer cells

被引:86
作者
Ng, Enders K. O. [1 ]
Li, Rufina [1 ]
Shin, Vivian Y. [1 ]
Siu, Jennifer M. [1 ]
Ma, Edmond S. K. [2 ]
Kwong, Ava [1 ,3 ,4 ]
机构
[1] Univ Hong Kong, Dept Surg, Hong Kong, Hong Kong, Peoples R China
[2] Hong Kong Sanat & Hosp, Dept Mol Pathol, Hong Kong, Hong Kong, Peoples R China
[3] Hong Kong Hereditary Breast Canc Family Registry, Hong Kong, Hong Kong, Peoples R China
[4] Univ Hong Kong, Breast Surg Div, Hong Kong, Hong Kong, Peoples R China
关键词
miR-143; DNMT3A; Breast cancer; Tumor suppressor; PTEN; TUMOR-SUPPRESSOR; ABERRANT METHYLATION; PROSTATE-CANCER; EXPRESSION; PROGRESSION; PTEN; PROMOTER; GENES; METASTASIS; PROGNOSIS;
D O I
10.1007/s13277-013-1341-7
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
MicroRNAs (miRNAs) are small non-protein-coding RNAs that regulate expression of a wide variety of genes including those involved in cancer development. Here, we investigate the role of miR-143 in breast cancer. In this study, we showed that miR-143 was frequently downregulated in 80 % of breast carcinoma tissues compared to their adjacent noncancerous tissues. Ectopic expression of miR-143 inhibited proliferation and soft agar colony formation of breast cancer cells and also downregulated DNA methyltransferase 3A (DNMT3A) expression on both mRNA and protein levels. Restoration of miR-143 expression in breast cancer cells reduces PTEN hypermethylation and increases TNFRSF10C methylation. DNMT3A was demonstrated to be a direct target of miR-143 by luciferase reporter assay. Furthermore, miR-143 expression was observed to be inversely correlated with DNMT3A mRNA and protein expression in breast cancer tissues. Our findings suggest that miR-143 regulates DNMT3A in breast cancer cells. These findings elucidated a tumor-suppressive role of miR-143 in epigenetic aberration of breast cancer, providing a potential development of miRNA-based treatment for breast cancer.
引用
收藏
页码:2591 / 2598
页数:8
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