The Long Non-Coding RNA PCAT-1 Promotes Prostate Cancer Cell Proliferation through cMyc

John R. Prensner, Wei Chen, Sumin Han, Matthew K. Iyer, Qi Cao, Vishal Kothari, Joseph R. Evans, Karen E. Knudsen, Michelle T. Paulsen, Mats Ljungman, Theodore S. Lawrence, Arul M. Chinnaiyan, Felix Y. Feng

Research output: Contribution to journalArticlepeer-review

159 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)900-908
Number of pages9
JournalNeoplasia (United States)
Volume16
Issue number11
DOIs
StatePublished - 2014

Keywords

  • 3'UTR
  • CMyc
  • Cell proliferation
  • LncRNA
  • PCAT-1

ASJC Scopus subject areas

  • Cancer Research

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