MicroRNA-203 Regulates Growth and Metastasis of Breast Cancer.
OBJECTIVE
MicroRNAs (MiRNAs) control many biological events and play critical roles in the development of tumor. Among all miRNAs, miR203 has been recently shown to have an inhibitory effect on prostate cancer. However, its involvement in the carcinogenesis of breast cancer has not been reported.


METHODS
We examined the levels of miR203 in the breast cancer from the patients compared to the paired normal breast tissue. We also examined the levels of miR203 in several commonly used breast cancer cell lines. The effects of overexpression or depletion of miR203 on breast cancer cell growth were analyzed by a MTT assay, and on breast cancer cell invasion were examined by a scratch wound healing assay and a transwell cell migration assay. MiR203-targeted genes were analyzed by Western blot.


RESULTS
We detected significantly lower levels of miR203 in the breast cancer from the patients compared to the paired normal breast tissue. Moreover, the levels of miR203 were significantly lower in breast cancer tissue from the patients with cancer metastasis. Decreased miR203 levels were detected in all examined breast cancer lines. Overexpression of miR203 inhibited breast cancer cell growth and invasion, while antisense-mediated inhibition of miR203 enhanced cancer cell growth and invasion. Further analyses show that miR203 may inhibit cell growth through decreasing cell-cycle activator cyclinD2 and CDK6, increasing cell-cycle suppressor p21 and p27, and increasing apoptosis-associated protein Bcl-2. MiR203 may also inhibit cell metastasis through suppressing matrix metalloproteinase 2 (MMP2), MMP7 and MMP9.


CONCLUSIONS
Our data thus highlight miR203 as a novel therapeutic target for breast cancer.
The Second Department of Oncology, the Second Hospital of Heibei Medical University, Shijiazhuang, China.
Shan
S
Zhao
Jinzhu
J
Han
Likang
L
Zheng
Zixin
Z
Yang
Li
L
Zhao
Yingqian
Y
Lv
D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D056742:Cyclin D2 / Q000235:genetics; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D061986:MCF-7 Cells; D008666:Metalloendopeptidases / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D054462:p21-Activated Kinases / Q000235:genetics
C080336:CCND2 protein, human; D056742:Cyclin D2; C546703:MIRN203 microRNA, human; D035683:MicroRNAs; D018809:Proliferating Cell Nuclear Antigen; C413374:p27 antigen; D054462:p21-Activated Kinases; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6; D008666:Metalloendopeptidases