Pathologically decreased miR-26a antagonizes apoptosis and facilitates carcinogenesis by targeting MTDH and EZH2 in breast cancer.
The role of miR-26a in carcinogenesis appears to be a complicated one, in the sense that both oncogenic and tumor suppressive effects were reported in cancers such as glioblastoma and hepatocellular carcinoma, respectively. Here, we report for the first time that miR-26a is downregulated in breast cancer specimens and cell lines and its transient transfection initiates apoptosis of breast cancer cell line MCF7 cells. Furthermore, retrovirus-delivered miR-26a impairs the in vitro colony forming and in vivo tumor-loading ability of MCF7 cells. Subsequently, MTDH and EZH2 are identified as two direct targets of miR-26a and they are significantly upregulated in breast cancer. MCF7 xenografts with exogenous miR-26a show that a decrease in expression of both MTDH and EZH2 is accompanied by an increase in apoptosis. Moreover, knockdown of MTDH causes apoptosis while reexpression of MTDH partially reverses the proapoptotic effect of miR-26a in MCF7 cells. Our findings suggest that miR-26a functionally antagonizes human breast carcinogenesis by targeting MTDH and EZH2.
Department of Pathophysiology, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, China.
Bo
B
Zhang
Xiao-Xiao
XX
Liu
Jian-Rong
JR
He
Ci-Xiang
CX
Zhou
Meng
M
Guo
Ming
M
He
Mei-Fang
MF
Li
Guo-Qiang
GQ
Chen
Qian
Q
Zhao
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D053938:DNA Fragmentation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D063151:Polycomb Repressive Complex 2; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D000071221:Enhancer of Zeste Homolog 2 Protein; D008565:Membrane Proteins; D035683:MicroRNAs; D063151:Polycomb Repressive Complex 2; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C528163:MIRN26 microRNA, human; C483039:MTDH protein, human; C498409:EZH2 protein, human