Blockade of invasion and metastasis of breast cancer cells via targeting CXCR4 with an artificial microRNA.
miRNAs have been shown to function as regulatory molecules and to play an important role in cancer progression. Very little is currently known about the increasing invasion and metastasis of breast cancer due to the loss of expressive levels of certain miRNAs in breast tumor cells. In order to determine whether the CXCR4/SDF-1 pathway is regulated by expression of miRNAs, we designed and synthesized pre-miRNA against CXCR4. This double-stranded miRNA gene was ligated with a miR-155-based Block-iT Pol II miR RNAi Expression Vector (Invitrogen). Expression levels of CXCR4 in CXCR4-miRNA-transfected breast tumor cells had significantly declined. These cells exhibited reduced migration and invasion in vitro. Furthermore, they formed fewer lung metastases in vivo compared to ctrl-miRNA-transfected cells. These data support the conclusion that miRNA against CXCR4 can serve as an alterative means of therapy to lower CXCR4 expression and to block the invasion and metastasis of breast cancer cells.
Liang
Zhongxing
Z
Department of Radiology, Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA. zliang@emory.edu
Wu
Hui
H
Reddy
Santosh
S
Zhu
Aizhi
A
Wang
Sijia
S
Blevins
Dean
D
Yoon
Younghyoun
Y
Zhang
Yawei
Y
Shim
Hyunsuk
H
D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000378:metabolism / Q000502:physiology; D015536:Down-Regulation; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000473:pathology / Q000628:therapy; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D023041:Xenograft Model Antitumor Assays / Q000379:methods
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D035683:MicroRNAs; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D051057:Proto-Oncogene Proteins c-akt