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Clin Cancer Res. 2011 Apr 1;17(7):1722-30. doi: 10.1158/1078-0432.CCR-10-1800. Epub 2011 Feb 24.

Analysis of MiR-195 and MiR-497 expression, regulation and role in breast cancer.

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  • 1Institute of Molecular and Chemical Biology, East China Normal University, Shanghai, China.

Abstract

PURPOSE:

To investigate expression, regulation, potential role and targets of miR-195 and miR-497 in breast cancer.

EXPERIMENTAL DESIGN:

The expression patterns of miR-195 and miR-497 were initially examined in breast cancer tissues and cell lines by Northern blotting and quantitative real-time PCR. Combined bisulfite restriction analysis and bisulfite sequencing were carried out to study the DNA methylation status of miR-195 and miR-497 genes. Breast cancer cells stably expressing miR-195 and miR-497 were established to study their role and targets. Finally, normal, fibroadenoma and breast cancer tissues were employed to analyze the correlation between miR-195/497 levels and malignant stages of breast tumor tissues.

RESULTS:

MiR-195 and miR-497 were significantly downregulated in breast cancer. The methylation state of CpG islands upstream of the miR-195/497 gene was found to be responsible for the downregulation of both miRNAs. Forced expression of miR-195 or miR-497 suppressed breast cancer cell proliferation and invasion. Raf-1 and Ccnd1 were identified as novel direct targets of miR-195 and miR-497. miR-195/497 expression levels in clinical specimens were found to be correlated inversely with malignancy of breast cancer.

CONCLUSIONS:

Our data imply that both miR-195 and miR-497 play important inhibitory roles in breast cancer malignancy and may be the potential therapeutic and diagnostic targets.

PMID:
21350001
[PubMed - indexed for MEDLINE]
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