Analysis of MiR-195 and MiR-497 Expression, Regulation and Role in Breast Cancer

被引：287

作者：

Li, Dan ^{[1
]}

Zhao, Yulan ^{[1
]}

Liu, Changxing ^{[2
]}

Chen, Xiaona ^{[1
]}

Qi, Yanting ^{[10
]}

Jiang, Yue ^{[1
,10
]}

Zou, Chao ^{[1
]}

Zhang, Xiaolong ^{[1
]}

Liu, Shunying ^{[1
]}

Wang, Xuejing ^{[6
,7
]}

Zhao, Dan ^{[1
]}

Sun, Qiang ^{[6
,7
]}

Zeng, Zhenbing ^{[3
,4
]}

Dress, Andreas ^{[3
,4
]}

Lin, Marie C. ^{[1
,9
]}

Kung, Hsiang-Fu ^{[1
,8
]}

Rui, Hallgeir ^{[10
]}

Liu, Ling-Zhi ^{[10
]}

Mao, Feng ^{[6
,7
]}

Jiang, Bing-Hua ^{[5
,10
]}

Lai, Lihui ^{[1
]}

机构：

[1] E China Normal Univ, Inst Mol & Chem Biol, Shanghai 200062, Peoples R China

[2] Fudan Univ, Dept Gen Surg, Huashan Hosp, Shanghai Med Coll, Shanghai, Peoples R China

[3] Chinese Acad Sci, CAS MPG Partner Inst, SIBS, Shanghai, Peoples R China

[4] Chinese Acad Sci, Key Lab Computat Biol, SIBS, Shanghai, Peoples R China

[5] Nanjing Med Univ, Dept Pathol, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Ctr Canc, Nanjing, Peoples R China

[6] Chinese Acad Med Sci, Dept Breast Surg, Peking Union Med Coll Hosp, Beijing 100037, Peoples R China

[7] Peking Union Med Coll, Beijing 100021, Peoples R China

[8] Chinese Univ Hong Kong, Fac Med, Shatin, Hong Kong, Peoples R China

[9] Chinese Univ Hong Kong, Brain Tumor Ctr, Div Neurosurg, Fac Med,PWH, Shatin, Hong Kong, Peoples R China

[10] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Kimmel Canc Ctr, Philadelphia, PA 19107 USA

来源：

CLINICAL CANCER RESEARCH | 2011年 / 17卷 / 07期

基金：

美国国家科学基金会;

关键词：

MICRORNA SIGNATURES; ACTIVATION; GENE;

D O I：

10.1158/1078-0432.CCR-10-1800

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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 miR195 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. Clin Cancer Res; 17(7); 1722-30. (C) 2011 AACR.

引用

页码：1722 / 1730

页数：9

共 35 条

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