title: Altered miRNA expression in high-fat diet-induced prostate cancer progression.
abstract: Recent evidence suggests that a high-fat diet (HFD) plays an important role in prostate carcinogenesis; however, underlying mechanisms largely remain unknown. Here, we investigated microRNA (miRNA) expression changes in murine prostate cancer (PCa) xenografts using two different diets: HFD and control diet. We then assessed the roles and targets of altered miRNAs in HFD-induced PCa progression. We identified 38 up- and 21 downregulated miRNAs in xenografts under HFD conditions using the miRCURY LNA™ microRNA array. The differences in 10 candidate miRNAs were validated using quantitative RT-PCR. We focused on miR-130a because the expression levels were significantly lower in the three PCa cell lines in comparison with benign prostate PINT1B cells. PCa cells cultured in a medium containing HFD mouse serum were associated with significantly higher cell proliferation rates and lower miR-130a expression levels. Further, miR-130a modulated MET expression in PCa cells, and MET was overexpressed in in vitro and in vivo HFD-induced PCa progression models. Moreover, ectopic miR-130a downregulated AR in LNCaP cells and DICER1 in PC-3 and DU145 cells, respectively. In human tissues, as elucidated using laser capture microdissection, the mean miR-130a expression level in cancer epithelium was significantly lower than that in normal epithelium. Furthermore, cytoplasmic MET in PCa tissues was overexpressed in patients with higher body mass index. In conclusion, a substantial number of miRNAs was altered in HFD-induced PCa growth. Specifically, miR-130a was attenuated in HFD-induced PCa progression with MET overexpression. miRNAs thus have implications in the mechanism, prevention and treatment of HFD-induced PCa progression.
authors.affiliation: Department of Urology and.
authors.forename: Taketoshi
authors.initials: T
authors.lastname: Nara
authors.affiliation: Department of Urology and nari6202@gipc.akita-u.ac.jp.|Department of Molecular Pathology and Tumor Pathology, Akita University School of Medicine, 1-1-1 Hondo, Akita, 010-8543 Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Narita
authors.affiliation: Department of Urology and.|Department of Molecular Pathology and Tumor Pathology, Akita University School of Medicine, 1-1-1 Hondo, Akita, 010-8543 Japan.
authors.forename: Huang
authors.initials: H
authors.lastname: Mingguo
authors.affiliation: Department of Urology, Yamagata University School of Medicine, Yamagata, 990-9585 Japan and.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Yoshioka
authors.affiliation: Department of Urology and.|Department of Molecular Pathology and Tumor Pathology, Akita University School of Medicine, 1-1-1 Hondo, Akita, 010-8543 Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Koizumi
authors.affiliation: Department of Urology and.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Numakura
authors.affiliation: Department of Urology and.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsuruta
authors.affiliation: Department of Urology and.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Maeno
authors.affiliation: Department of Urology and.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Saito
authors.affiliation: Department of Urology and.|Department of Molecular Pathology and Tumor Pathology, Akita University School of Medicine, 1-1-1 Hondo, Akita, 010-8543 Japan.
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Inoue
authors.affiliation: AMED-CREST, Japan Agency for Medical Research and Development (AMED).
authors.forename: Norihiko
authors.initials: N
authors.lastname: Tsuchiya
authors.affiliation: Department of Urology and.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Satoh
authors.affiliation: Department of Urology and.|Department of Molecular Pathology and Tumor Pathology, Akita University School of Medicine, 1-1-1 Hondo, Akita, 010-8543 Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Habuchi
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D059305:Diet, High-Fat / Q000009:adverse effects; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D011471:Prostatic Neoplasms / Q000178:diet therapy / Q000235:genetics* / Q000473:pathology; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C554019:MIRN130 microRNA, human; D035683:MicroRNAs; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met