Systemic delivery of synthetic microRNA-16 inhibits the growth of metastatic prostate tumors via downregulation of multiple cell-cycle genes.
Recent reports have linked the expression of specific microRNAs (miRNAs) with tumorigenesis and metastasis. Here, we show that microRNA (miR)-16, which is expressed at lower levels in prostate cancer cells, affects the proliferation of human prostate cancer cell lines both in vitro and in vivo. Transient transfection with synthetic miR-16 significantly reduced cell proliferation of 22Rv1, Du145, PPC-1, and PC-3M-luc cells. A prostate cancer xenograft model revealed that atelocollagen could efficiently deliver synthetic miR-16 to tumor cells on bone tissues in mice when injected into tail veins. In the therapeutic bone metastasis model, injection of miR-16 with atelocollagen via tail vein significantly inhibited the growth of prostate tumors in bone. Cell model studies indicate that miR-16 likely suppresses prostate tumor growth by regulating the expression of genes such as CDK1 and CDK2 associated with cell-cycle control and cellular proliferation. There is a trend toward lower miR-16 expression in human prostate tumors versus normal prostate tissues. Thus, this study indicates the therapeutic potential of miRNA in an animal model of cancer metastasis with systemic miRNA injection and suggest that systemic delivery of miR-16 could be used to treat patients with advanced prostate cancer.
Takeshita
Fumitaka
F
Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo, Japan.
Patrawala
Lubna
L
Osaki
Mitsuhiko
M
Takahashi
Ryou-u
RU
Yamamoto
Yusuke
Y
Kosaka
Nobuyoshi
N
Kawamata
Masaki
M
Kelnar
Kevin
K
Bader
Andreas G
AG
Brown
David
D
Ochiya
Takahiro
T
D000368:Aged; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000627:therapeutic use*; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018797:Cell Cycle Proteins; D035683:MicroRNAs