title: miR-409-3p/-5p promotes tumorigenesis, epithelial-to-mesenchymal transition, and bone metastasis of human prostate cancer.
abstract: OBJECTIVE
  miR-409-3p/-5p is a miRNA expressed by embryonic stem cells, and its role in cancer biology and metastasis is unknown. Our pilot studies demonstrated elevated miR-409-3p/-5p expression in human prostate cancer bone metastatic cell lines; therefore, we defined the biologic impact of manipulation of miR-409-3p/-5p on prostate cancer progression and correlated the levels of its expression with clinical human prostate cancer bone metastatic specimens.
  
  
  METHODS
  miRNA profiling of a prostate cancer bone metastatic epithelial-to-mesenchymal transition (EMT) cell line model was performed. A Gleason score human tissue array was probed for validation of specific miRNAs. In addition, genetic manipulation of miR-409-3p/-5p was performed to determine its role in tumor growth, EMT, and bone metastasis in mouse models.
  
  
  RESULTS
  Elevated expression of miR-409-3p/-5p was observed in bone metastatic prostate cancer cell lines and human prostate cancer tissues with higher Gleason scores. Elevated miR-409-3p expression levels correlated with progression-free survival of patients with prostate cancer. Orthotopic delivery of miR-409-3p/-5p in the murine prostate gland induced tumors where the tumors expressed EMT and stemness markers. Intracardiac inoculation (to mimic systemic dissemination) of miR-409-5p inhibitor-treated bone metastatic ARCaPM prostate cancer cells in mice led to decreased bone metastasis and increased survival compared with control vehicle-treated cells.
  
  
  CONCLUSIONS
  miR-409-3p/-5p plays an important role in prostate cancer biology by facilitating tumor growth, EMT, and bone metastasis. This finding bears particular translational importance as miR-409-3p/-5p appears to be an attractive biomarker and/or possibly a therapeutic target to treat bone metastatic prostate cancer.
authors: Uro-Oncology Research Program, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California. leland.chung@cshs.org Sajni.Josson@cshs.org Murali.Gururajan@cshs.org.
authors: Sajni
authors: S
authors: Josson
authors: Uro-Oncology Research Program, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California. leland.chung@cshs.org Sajni.Josson@cshs.org Murali.Gururajan@cshs.org.
authors: Murali
authors: M
authors: Gururajan
authors: Uro-Oncology Research Program, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California.
authors: Peizhen
authors: P
authors: Hu
authors: Uro-Oncology Research Program, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California.
authors: Chen
authors: C
authors: Shao
authors: Uro-Oncology Research Program, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California.
authors: GinaChia-Yi
authors: GY
authors: Chu
authors: Uro-Oncology Research Program, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California.
authors: Haiyen E
authors: HE
authors: Zhau
authors: Uro-Oncology Research Program, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California.
authors: Chunyan
authors: C
authors: Liu
authors: Genetic Systems, Life Technologies Inc., South San Francisco, California.
authors: Kaiqin
authors: K
authors: Lao
authors: Uro-Oncology Research Program, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California.
authors: Chia-Lun
authors: CL
authors: Lu
authors: Uro-Oncology Research Program, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California.
authors: Yi-Tsung
authors: YT
authors: Lu
authors: Uro-Oncology Research Program, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California.
authors: Jake
authors: J
authors: Lichterman
authors: Uro-Oncology Research Program, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California.
authors: Srinivas
authors: S
authors: Nandana
authors: Biostatistics and Bioinformatics, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California.
authors: Quanlin
authors: Q
authors: Li
authors: Biostatistics and Bioinformatics, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California.
authors: Andre
authors: A
authors: Rogatko
authors: Biostatistics and Bioinformatics, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California.
authors: Dror
authors: D
authors: Berel
authors: Uro-Oncology Research Program, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California.
authors: Edwin M
authors: EM
authors: Posadas
authors: Vancouver Prostate Cancer Center, University of British Columbia, Vancouver, Canada.
authors: Ladan
authors: L
authors: Fazli
authors: Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California.
authors: Dhruv
authors: D
authors: Sareen
authors: Uro-Oncology Research Program, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California. leland.chung@cshs.org Sajni.Josson@cshs.org Murali.Gururajan@cshs.org.
authors: Leland W K
authors: LW
authors: Chung
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D011471:Prostatic Neoplasms
chemical_list: C572367:MIRN409 microRNA, human; D035683:MicroRNAs