Faculty Collaboration Database

Analysis of MiR-195 and MiR-497 expression, regulation and role in breast cancer. Clin Cancer Res 2011 Apr 01;17(7):1722-30

Date

02/26/2011

Pubmed ID

21350001

DOI

10.1158/1078-0432.CCR-10-1800

Scopus ID

2-s2.0-79953330808 (requires institutional sign-in at Scopus site)   284 Citations

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.

Author List

Li D, Zhao Y, Liu C, Chen X, Qi Y, Jiang Y, Zou C, Zhang X, Liu S, Wang X, Zhao D, Sun Q, Zeng Z, Dress A, Lin MC, Kung HF, Rui H, Liu LZ, Mao F, Jiang BH, Lai L

MESH terms used to index this publication - Major topics in bold

3' Untranslated Regions
Base Sequence
Breast Neoplasms
Cell Line, Tumor
Cell Movement
Cell Proliferation
CpG Islands
Cyclin D1
DNA Methylation
Down-Regulation
Female
Gene Silencing
Genes, Reporter
Humans
Luciferases, Renilla
MicroRNAs
Neoplasm Invasiveness
Proto-Oncogene Proteins c-raf
Restriction Mapping