Restoration of miR-145 expression suppresses cell proliferation, migration and invasion in prostate cancer by targeting FSCN1.
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression, primarily at the post-transcriptional level. Growing evidence suggests that miRNAs function as oncogenes or tumor suppressors in human cancers. The down-regulation of miR-145 has been reported in many types of human cancer, including prostate cancer (PC), suggesting that miR-145 functions as a tumor suppressor. Using the PC cell lines, PC3 and DU145, gain-of-function assays revealed that miR-145 transfection inhibited cell proliferation, migration and invasion. Fascin homolog 1 (FSCN1), an actin-bundling protein, is a candidate target gene of miR-145 based on genome-wide gene expression analysis. A luciferase reporter assay showed a significantly decreased signal at two miR-145 target sites at the 3'UTR of FSCN1, suggesting that miR-145 directly regulates FSCN1. In FSCN1 loss-of-function assays, cell growth, migration and invasion were all inhibited, implying that FSCN1 is associated with the progression of PC. The identification of tumor suppressive miRNAs and their target genes could provide new insights into the potential mechanisms of prostate carcinogenesis.
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
Miki
M
Fuse
Nijiro
N
Nohata
Satoko
S
Kojima
Shinichi
S
Sakamoto
Takeshi
T
Chiyomaru
Kazumori
K
Kawakami
Hideki
H
Enokida
Masayuki
M
Nakagawa
Yukio
Y
Naya
Tomohiko
T
Ichikawa
Naohiko
N
Seki
D020413:3' Untranslated Regions; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D017930:Genes, Reporter; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics*; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics
D020413:3' Untranslated Regions; D002352:Carrier Proteins; C502658:FSCN1 protein, human; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D008840:Microfilament Proteins; D034741:RNA, Small Interfering