Yong Liu, Jing Zhao, Pei-Ying Zhang, Yu Zhang, San-Yuan Sun, Shi-Ying Yu, Qing-Song Xi
Med Sci Monit 2012; 18(8): BR299-308
Available online: 2012-08-01
Background: Recent studies have suggested that microRNA-10b (miR-10b) acts as a promoter of metastasis in breast cancer, although the underlying mechanism remains largely unknown. In this study, we provide the first evidence that E-cadherin (E-cad) is a potential target of miR-10b.
Material/Method: By applying gain-of-function and loss-of-function approaches in the metastatic breast cancer cell line MDA-MB-231, we demonstrated that miR-10b is necessary and sufficient to regulate the cellular expression of E-cad and in vitro tumor cell invasion.
Results: Comparative expression analysis of miR-10b in benign breast lesions (N=16), primary breast cancers (N=21), and metastatic breast carcinomas (N=23) revealed that miR-10b transcription was uniquely up-regulated in metastatic cancers. The expression level of miR-10b positively correlated with tumor size, pathological grading, clinical staging, lymph node metastasis, Her2-positivity and tumor proliferation, but was negatively associated with estrogen receptor-positivity, progesterone receptor-positivity and E-cad mRNA and protein levels.
Conclusions: These findings indicate the existence of a novel E-cadherin-related mechanism by which miR-10b modulates breast cancer metastasis. In addition, miR-10b may be a useful biomarker of advanced progression and metastasis of breast cancer.
Keywords: Molecular Sequence Data, MicroRNAs - metabolism, Linear Models, Gene Expression Regulation, Neoplastic, Down-Regulation, Cell Line, Tumor, Cadherins - metabolism, Breast Neoplasms - pathology, Base Sequence, Adult, Multivariate Analysis, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasm Staging, Up-Regulation - genetics