Regulation of metastasis-promoting LOXL2 gene expression by antitumor microRNAs in prostate cancer.
Our recent studies of microRNA (miRNA) expression signatures of prostate cancer (PCa) showed that six miRNAs (specifically, miR-26a, miR-26b, miR-29a, miR-29b, miR-29c and miR-218) were markedly reduced in cancer tissues. Moreover, ectopic expression of these miRNAs suppressed PCa cell aggressiveness, indicating that these miRNAs acted in concert to regulate genes that promoted metastasis. Genome-wide gene expression analysis and in silico database analysis identified a total of 35 candidate genes that promoted metastasis and were targeted by these 6 miRNAs. Using luciferase reporter assays, we showed that the lysyl oxidase-like 2 (LOXL2) gene was directly controlled by these tumor-suppressive miRNAs in PCa cells. Overexpression of LOXL2 was confirmed in PCa tissues and knockdown of the LOXL2 gene markedly inhibited the migration and invasion of PCa cells. Aberrant expression of LOXL2 enhanced migration and invasion of PCa cells. Downregulation of antitumor miRNAs might disrupt the tightly controlled RNA networks found in normal cells. New insights into the novel molecular mechanisms of PCa pathogenesis was revealed by antitumor miRNA-regulated RNA networks.
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.|Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan.
Mayuko
M
Kato
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.|Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan.
Akira
A
Kurozumi
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.|Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan.
Yusuke
Y
Goto
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Ryosuke
R
Matsushita
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.|Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan.
Atsushi
A
Okato
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.|Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan.
Rika
R
Nishikawa
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
Ichiro
I
Fukumoto
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
Keiichi
K
Koshizuka
Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan.
Tomohiko
T
Ichikawa
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
Naohiko
N
Seki
D020413:3' Untranslated Regions / Q000235:genetics; D000594:Amino Acid Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid
D020413:3' Untranslated Regions; D000594:Amino Acid Oxidoreductases; D035683:MicroRNAs; C547471:MIRN218 microRNA, human; C528163:MIRN26 microRNA, human; C532045:MIRN29a microRNA, human; C119091:LOXL2 protein, human