MicroRNA-143 is downregulated in breast cancer and regulates DNA methyltransferases 3A in breast cancer cells.
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.
Department of Surgery, The University of Hong Kong, Hong Kong SAR, Hong Kong.
Enders K O
EK
Ng
Rufina
R
Li
Vivian Y
VY
Shin
Jennifer M
JM
Siu
Edmond S K
ES
Ma
Ava
A
Kwong
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000096:biosynthesis* / Q000235:genetics; D019175:DNA Methylation / Q000502:physiology; D000090205:DNA Methyltransferase 3A; D015536:Down-Regulation; D044127:Epigenesis, Genetic / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
C000717967:DNMT3A protein, human; C542359:MIRN143 microRNA, human; D035683:MicroRNAs; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A