title: The long non-coding RNA PCAT-1 promotes prostate cancer cell proliferation through cMyc.
abstract: Long non-coding RNAs (lncRNAs) represent an emerging layer of cancer biology, contributing to tumor proliferation, invasion, and metastasis. Here, we describe a role for the oncogenic lncRNA PCAT-1 in prostate cancer proliferation through cMyc. We find that PCAT-1-mediated proliferation is dependent on cMyc protein stabilization, and using expression profiling, we observed that cMyc is required for a subset of PCAT-1-induced expression changes. The PCAT-1-cMyc relationship is mediated through the post-transcriptional activity of the MYC 3' untranslated region, and we characterize a role for PCAT-1 in the disruption of MYC-targeting microRNAs. To further elucidate a role for post-transcriptional regulation, we demonstrate that targeting PCAT-1 with miR-3667-3p, which does not target MYC, is able to reverse the stabilization of cMyc by PCAT-1. This work establishes a basis for the oncogenic role of PCAT-1 in cancer cell proliferation and is the first study to implicate lncRNAs in the regulation of cMyc in prostate cancer.
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Prensner
authors.affiliation: Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Sumin
authors.initials: S
authors.lastname: Han
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Iyer
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA ; Department of Pathology, University of Michigan Medical School,Ann Arbor, MI, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Cao
authors.affiliation: Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Vishal
authors.initials: V
authors.lastname: Kothari
authors.affiliation: Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Evans
authors.affiliation: Department of Cancer Biology, Thomas Jefferson University, Philadelphia, PA, USA ; Department of Urology, Thomas Jefferson University, Philadelphia, PA, USA ; Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Knudsen
authors.affiliation: Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA ; Translational Oncology Program, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Michelle T
authors.initials: MT
authors.lastname: Paulsen
authors.affiliation: Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA ; Translational Oncology Program, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Mats
authors.initials: M
authors.lastname: Ljungman
authors.affiliation: Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Lawrence
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA ; Department of Pathology, University of Michigan Medical School,Ann Arbor, MI, USA ; Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA ; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA ; Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA ; Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA ; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Felix Y
authors.initials: FY
authors.lastname: Feng
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020413:3' Untranslated Regions; C489427:MYC protein, human; D035683:MicroRNAs; C588212:PCAT-1 lncRNA, human; D016271:Proto-Oncogene Proteins c-myc; D062085:RNA, Long Noncoding
keywords: 3’UTR; PCAT-1; cMyc; cell proliferation; lncRNA