title: Transforming growth factor-β promotes prostate bone metastasis through induction of microRNA-96 and activation of the mTOR pathway.
abstract: Transforming growth factor-β (TGFβ) is enriched in the bone matrix and serves as a key factor in promoting bone metastasis in cancer. In addition, TGFβ signaling activates mammalian target of rapamycin (mTOR) functions, which is important for the malignant progression. Here, we demonstrate that TGFβ regulates the level of microRNA-96 (miR-96) through Smad-dependent transcription and that miR-96 promotes the bone metastasis in prostate cancer. The enhanced effects in cellular growth and invasiveness suggest that miR-96 functions as an oncomir/and metastamir. Supporting this idea, we identified a downstream target of the TGFβ-miR-96 signaling pathway to be AKT1S1 mRNA, whose translated protein is a negative regulator of mTOR kinase. Our findings provide a novel mechanism accounting for the TGFβ signaling and bone metastasis.
authors.affiliation: Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, Taiwan.|Department of Anesthesiology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: M K
authors.initials: MK
authors.lastname: Siu
authors.affiliation: Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, Taiwan.|Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Tsai
authors.affiliation: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Y-S
authors.initials: YS
authors.lastname: Chang
authors.affiliation: Cell and Cancer Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Yin
authors.affiliation: Cell and Cancer Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: F
authors.initials: F
authors.lastname: Suau
authors.affiliation: Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: W-Y
authors.initials: WY
authors.lastname: Chen
authors.affiliation: Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, Taiwan.|Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Y-N
authors.initials: YN
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D051785:Smad Proteins / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C484523:AKT1S1 protein, human; D048868:Adaptor Proteins, Signal Transducing; C541492:MIRN96 microRNA, human; D035683:MicroRNAs; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases