MiR-124 inhibits cell proliferation in breast cancer through downregulation of CDK4.
Studies have shown that microRNAs (miRNAs) are involved in the malignant progression of human cancer. However, little is known about the potential role of miRNAs in breast carcinogenesis. miR-124 expression in breast cancer tissue was measured by quantitative real-time PCR (qRT-PCR). Target prediction algorithms and luciferase reporter gene assays were used to investigate the target of miR-124. Breast cancer cells growth was regulated by overexpression or knockdown miR-124. At the end of the study, tumor-bearing mice were tested to confirm the function of miR-124 in breast cancer. In this study, we demonstrated that the expression of miR-124 was significantly downregulated in breast cancer tissues compared with matched adjacent non-neoplastic tissues. We identified and confirmed that cyclin-dependent kinase 4 (CDK4) was a direct target of miR-124. Overexpression of miR-124 suppressed CDK4 protein expression and attenuated cell viability, proliferation, and cell cycle progression in MCF-7 and MDA-MB-435S breast cancer cells in vitro. Overexpression of CDK4 partially rescued the inhibitory effect of miR-124 in the breast cancer cells. Moreover, we found that miR-124 overexpression effectively repressed tumor growth in xenograft animal experiments. Our results demonstrate that miR-124 functions as a growth-suppressive miRNA and plays an important role in inhibiting tumorigenesis by targeting CDK4.
Oncology Institute, The Affiliated Hospital of Nanjing Medical University, Changzhou No.2 People's Hospital, Changzhou, 213003, China.
Tongbao
T
Feng
Dongqin
D
Xu
Chao
C
Tu
Wenjing
W
Li
Yongling
Y
Ning
Jun
J
Ding
Shizhong
S
Wang
Liudi
L
Yuan
Ning
N
Xu
Keqing
K
Qian
Yong
Y
Wang
Chunjian
C
Qi
D020413:3' Untranslated Regions; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D051358:Cyclin-Dependent Kinase 4 / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D034622:RNA Interference
D020413:3' Untranslated Regions; C509207:MIRN124 microRNA, human; D035683:MicroRNAs; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4