miR-1207-3p regulates the androgen receptor in prostate cancer via FNDC1/fibronectin.
Prostate cancer (PCa) is frequently diagnosed in men, and dysregulation of microRNAs is characteristic of many cancers. MicroRNA-1207-3p is encoded at the non-protein coding gene locus PVT1 on the 8q24 human chromosomal region, an established PCa susceptibility locus. However, the role of microRNA-1207-3p in PCa is unclear. We discovered that microRNA-1207-3p is significantly underexpressed in PCa cell lines in comparison to normal prostate epithelial cells. Increased expression of microRNA-1207-3p in PCa cells significantly inhibits proliferation, migration, and induces apoptosis via direct molecular targeting of FNDC1, a protein which contains a conserved protein domain of fibronectin (FN1). FNDC1, FN1, and the androgen receptor (AR) are significantly overexpressed in PCa cell lines and human PCa, and positively correlate with aggressive PCa. Prostate tumor FN1 expression in patients that experienced PCa-specific death is significantly higher than in patients that remained alive. Furthermore, FNDC1, FN1 and AR are concomitantly overexpressed in metastatic PCa. Consequently, these studies have revealed a novel microRNA-1207-3p/FNDC1/FN1/AR regulatory pathway in PCa.
Department of Biological Sciences, Hunter College of The City University of New York, New York, NY 10065, USA; The Graduate Center Departments of Biology and Biochemistry, The City University of New York, New York, NY 10016, USA; Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA.
Dibash K
DK
Das
Department of Biological Sciences, Hunter College of The City University of New York, New York, NY 10065, USA.
Michelle
M
Naidoo
Department of Biological Sciences, Hunter College of The City University of New York, New York, NY 10065, USA.
Adeodat
A
Ilboudo
Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612, USA.
Jong Y
JY
Park
Department of Biological Sciences, Hunter College of The City University of New York, New York, NY 10065, USA.
Thahmina
T
Ali
Department of Biological Sciences, Hunter College of The City University of New York, New York, NY 10065, USA; Department of Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA.
Konstantinos
K
Krampis
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA; Department of Urology, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA.
Brian D
BD
Robinson
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Joseph R
JR
Osborne
Department of Biological Sciences, Hunter College of The City University of New York, New York, NY 10065, USA; The Graduate Center Departments of Biology and Biochemistry, The City University of New York, New York, NY 10016, USA; Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA. Electronic address: ogunwobi@genectr.hunter.cuny.edu.
Olorunseun O
OO
Ogunwobi
D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
C410798:AR protein, human; C067625:FN1 protein, human; C505811:FNDC1 protein, human; D005353:Fibronectins; C575047:MIRN1207 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D011944:Receptors, Androgen
Androgen receptor; Fibronectin; Fibronectin type III domain containing 1; MiR-1207-3p; Prostate cancer
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