Elsevier

Neoplasia

Volume 16, Issue 11, November 2014, Pages 900-908
Neoplasia

The Long Non-Coding RNA PCAT-1 Promotes Prostate Cancer Cell Proliferation through cMyc1,2

https://doi.org/10.1016/j.neo.2014.09.001Get rights and content
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open access

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.

Keywords

PCAT-1
lncRNA
cell proliferation
3’UTR
cMyc

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1

This article refers to supplementary materials, which are designated by Tables W1 to W9 and Figures W1 to W8 and are available online at www.neoplasia.com.

2

This work was supported in part by the Prostate Cancer Foundation (F.Y.F. and A.M.C.), the Prostate Cancer Foundation Young Investigator Award (J.R.P. and Q.C.), National Institutes of Health Prostate Specialized Program of Research Excellence grant P50CA69568, Department of Defense grants PC094231 (F.Y.F.) and PC100171 (A.M.C.), the Early Detection Research Network grant UO1 CA111275 (A.M.C.), the US National Institutes of Health R01CA132874-01A1 (A.M.C.), and the National Center for Functional Genomics support by the Department of Defense (to A.M.C.). A.M.C. is also supported by the Doris Duke Charitable Foundation Clinical Scientist Award and the Howard Hughes Medical Institute. A.M.C. is an American Cancer Society Research Professor and a Taubman Scholar of the University of Michigan. J.R.P., M.K.I, and Q.C. were supported by the Department of Defense Fellowship grants PC094290 (to J.R.P), BC100238 (to M.K.I.), and PC094725 (to Q.C.). The University of Michigan has filed a patent on PCAT-1 in which A.M.C., J.R.P., and M.K.I. are named as co-inventors. Wafergen, Inc has a non-exclusive license for creating commercial research assays for the detection of lncRNAs including PCAT-1. A.M.C. serves on the Scientific Advisory Board of Wafergen. Gen-Probe or Wafergen had no role in the design or experimentation of this study nor has it participated in the writing of the manuscript. Gene expression array data: Microarray data have been deposited at the NCBI Gene Expression Omnibus as GSE54872. Microarray data will be made available on publication. Author contributions: J.R.P., W.C., A.M.C., and F.Y.F. designed the project and directed the experimental studies. W.C., J.R.P., Q.C., M.T.P., V.K., S.H., J.R.E., and M.L. performed the experimental studies. M.K.I. performed the bioinformatics and statistical analyses. J.R.P. and M.K.I. performed the microRNA analyses. T.S.L., K.E.K., and M.L. facilitated the experiments and interpreted the data. J.R.P., W.C., and F.Y.F. interpreted the data and wrote the manuscript.

3

These authors contributed equally.

4

Current address: Center for Inflammation and Epigenetics, Methodist Cancer Center, Houston Methodist Research Institute, Houston, TX 77030.