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Analysis of MiR-195 and MiR-497 expression, regulation and role in breast cancer.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2011 Apr 01; Vol. 17 (7), pp. 1722-30. Date of Electronic Publication: 2011 Feb 24. - Publication Year :
- 2011
-
Abstract
- Purpose: To investigate expression, regulation, potential role and targets of miR-195 and miR-497 in breast cancer.<br />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.<br />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.<br />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.
- Subjects :
- 3' Untranslated Regions
Base Sequence
Breast Neoplasms metabolism
Breast Neoplasms pathology
Cell Line, Tumor
Cell Movement
Cell Proliferation
CpG Islands
Cyclin D1 metabolism
DNA Methylation
Down-Regulation
Female
Gene Silencing
Genes, Reporter
Humans
Luciferases, Renilla biosynthesis
Luciferases, Renilla genetics
MicroRNAs metabolism
Neoplasm Invasiveness
Proto-Oncogene Proteins c-raf metabolism
Restriction Mapping
Breast Neoplasms genetics
MicroRNAs genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3265
- Volume :
- 17
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 21350001
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-10-1800