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

Abstract

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.

• Authors: Enders K O Ng, Rufina Li, Vivian Y Shin, Jennifer M Siu, Edmond S K Ma, Ava Kwong
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 35 Issue 3 Pg. 2591-8 (Mar 2014) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 24218337 (Publication Type: Journal Article)

Chemical References

• DNMT3A protein, human
• MIRN143 microRNA, human
• MicroRNAs
• DNA (Cytosine-5-)-Methyltransferases
• DNA Methyltransferase 3A

Topics

• Blotting, Western
• Breast Neoplasms (genetics, metabolism)
• Cell Line, Tumor
• Cell Proliferation
• DNA (Cytosine-5-)-Methyltransferases (biosynthesis, genetics)
• DNA Methylation (physiology)
• DNA Methyltransferase 3A
• Down-Regulation
• Epigenesis, Genetic (physiology)
• Female
• Gene Expression Regulation, Neoplastic (genetics)
• Humans
• MicroRNAs (biosynthesis)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Transfection