miR-145 inhibits breast cancer cell growth through RTKN.
MicroRNAs (miRNAs) represent a class of small non-coding RNAs regulating gene expression by inducing RNA degradation or interfering with translation. Aberrant miRNA expression has been described for several human malignancies. Herein, we show that miR-145 is down-regulated in human cancer cell line MCF-7 when compared to normal human mammary epithelial cell line MCF10A. Overexpression of miR-145 by plasmid inhibits MCF-7 cell growth and induces apoptosis. Subsequently, RTKN is identified as a potential miR-145 target by bioinformatics. Using reporter constructs, we show that the RTKN 3' untranslated region (3'UTR) carries the directly binding site of miR-145. Additionally, overexpression of miR-145 in MCF-7 reduces RTKN protein expression as well as mRNA level. Furthermore, down-regulation of RTKN by siRNA can inhibit MCF-7 cell growth. Taken together, we propose that loss of miR-145 may provide a selective growth advantage for MCF-7 by targeting RTKN.
Wang
Shihua
S
Center of Tissue Engineering, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, P.R. China.
Bian
Chunjing
C
Yang
Zhuo
Z
Bo
Ye
Y
Li
Jing
J
Zeng
Lifen
L
Zhou
Hong
H
Zhao
Robert Chunhua
RC
D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D019204:GTP-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D034741:RNA, Small Interfering / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; C100494:RTKN protein, human; D019204:GTP-Binding Proteins