Genetic heterogeneity of breast cancer metastasis may be related to miR-21 regulation of TIMP-3 in translation.
OBJECTIVE
MicroRNAs are noncoding RNA molecules that posttranscriptionally regulated expression of target gene and implicate the progress of cancer proliferation, differentiation, and apoptosis. The aim of this study is to determine whether microRNA-21 (miR-21), a specific microRNA implicated in multiple aspects of carcinogenesis, promoted breast cancer metastasis by regulating the tissue inhibitor of metalloproteinase 3 (TIMP-3) gene.


METHODS
miR-21 of serum and tissue from 40 patients (30 patients with breast cancer) were detected by real-time quantitative reverse transcriptase polymerase chain reaction (RT-qPCR). TIMP-3 of tissue from the patient was tested by real-time RT-qPCR. Protein expression of TIMP-3 was evaluated by western blotting. Correlation analysis was performed between miR-21 and TIMP-3.


RESULTS
Of the 40 samples from tissue and serum analyzed, the miR-21 expression was significantly higher in high invasion metastasis group (HIMG) that in low invasion metastasis group (LIMG); the latter was higher than that in normal group (NG). Additionally, the TIMP-3 expression was significantly lower in HIMG than in LIMG; the latter was lower than that in NG. There was significantly inverse correlation between miR-21 and TIMP-3 extracted from tissue.


CONCLUSIONS
Our data suggest that miR-21 could promote metastasis in breast cancer via the regulation of TIMP3 translation, and there was consistency between miR-21 of serum and miR-21 in tissue.
Department of Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China.
Jianyi
J
Li
Yang
Y
Zhang
Wenhai
W
Zhang
Shi
S
Jia
Rui
R
Tian
Ye
Y
Kang
Yan
Y
Ma
Dan
D
Li
D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018740:Genetic Heterogeneity; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3