MicroRNA-33b Inhibits Breast Cancer Metastasis by Targeting HMGA2, SALL4 and Twist1.
MicroRNAs are a class of small noncoding RNAs that regulate gene expression post-transcriptionally either by inhibiting protein translation or by causing the degradation of target mRNAs. Current evidence indicates that miR-33b is involved in the regulation of lipid metabolism, cholesterol homeostasis, glucose metabolism and several human diseases; however, whether miR-33b contributes to the pathogenesis of human cancers and participates in the regulation of self-renewal of human cancer stem cells remains unknown. Here, we report the identification of miR-33b as a negative regulator of cell stemness and metastasis in breast cancer. Compared with paired normal breast tissues, miR-33b expression is downregulated in breast tumor samples and is inversely correlated with lymph node metastatic status. Ectopic overexpression of miR-33b in highly metastatic breast cancer cells suppresses cell self-renewal, migration and invasion in vitro and inhibits lung metastasis in vivo. Conversely, miR-33b knockdown promotes the self-renewal, migration and invasion capabilities of noncancerous mammary epithelial cells. The mechanism through which miR-33b inhibits the stemness, migration and invasion of breast cancer cells is by targeting HMGA2, SALL4 and Twist1. These data indicate that miR-33b acts as an onco-suppressive microRNA in breast cancer progression by inhibiting the stemness and metastasis of breast cancer cells.
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102, China.
Yancheng
Y
Lin
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102, China.
Allan Yi
AY
Liu
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102, China.
Chuannan
C
Fan
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102, China.
Hong
H
Zheng
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102, China.
Yuan
Y
Li
Department of Surgical Oncology, First Affiliated Hospital of Xiamen University, Xiamen 361003, China.
Chuankai
C
Zhang
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102, China.
Shasha
S
Wu
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102, China.
Donghong
D
Yu
Department of Surgical Oncology, First Affiliated Hospital of Xiamen University, Xiamen 361003, China.
Zhengjie
Z
Huang
Medical College, Xiamen University, Xiamen 361102, China.
Fan
F
Liu
Department of Surgical Oncology, First Affiliated Hospital of Xiamen University, Xiamen 361003, China.
Qi
Q
Luo
College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
Chaoyong James
CJ
Yang
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102, China.
Gaoliang
G
Ouyang
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000556:secondary*; D005260:Female; D025743:HMGA2 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*
D025743:HMGA2 Protein; C550416:MIRN33a microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; C472575:SALL4 protein, human; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1