The lncRNA DRAIC/PCAT29 locus constitutes a tumor-suppressive nexus

Kohei Sakurai, Brian J. Reon, Jordan Anaya, Anindya Dutta

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Long noncoding RNAs (lncRNA) are emerging as major regulators of cellular phenotypes and implicated as oncogenes or tumor suppressors. Here, we report a novel tumor-suppressive locus on human chromosome 15q23 that contains two multiexonic lncRNA genes of 100 kb each: DRAIC (LOC145837) and the recently reported PCAT29. The DRAIC lncRNA was identified from RNA-seq data and is downregulated as prostate cancer cells progress from an androgen-dependent (AD) to a castration-resistant (CR) state. Prostate cancers persisting in patients after androgen deprivation therapy (ADT) select for decreased DRAIC expression, and higher levels of DRAIC in prostate cancer are associated with longer disease-free survival (DFS). Androgen induced androgen receptor (AR) binding to the DRAIC locus and repressed DRAIC expression. In contrast, FOXA1 and NKX3-1 are recruited to the DRAIC locus to induce DRAIC, and FOXA1 specifically counters the repression of DRAIC by AR. The decrease of FOXA1 and NKX3-1, and aberrant activation of AR, thus accounts for the decrease of DRAIC during prostate cancer progression to the CR state. Consistent with DRAIC being a good prognostic marker, DRAIC prevents the transformation of cuboidal epithelial cells to fibroblast-like morphology and prevents cellular migration and invasion. A second tumor-suppressive lncRNA PCAT29, located 20 kb downstream of DRAIC, is regulated identically by AR and FOXA1 and also suppresses cellular migration and metastasis. Finally, based on TCGA analysis, DRAIC expression predicts good prognosis in a wide range of malignancies, including bladder cancer, low-grade gliomas, lung adenocarcinoma, stomach adenocarcinoma, renal clear cell carcinoma, hepatocellular carcinoma, skin melanoma, and stomach adenocarcinoma. Implications: This study reveals a novel tumor-suppressive locus encoding two hormone-regulated lncRNAs, DRAIC and PCAT29, that are prognostic for a wide variety of cancer types.

Original languageEnglish
Pages (from-to)828-838
Number of pages11
JournalMolecular Cancer Research
Volume13
Issue number5
DOIs
Publication statusPublished - 01-01-2015
Externally publishedYes

Fingerprint

Long Noncoding RNA
Androgen Receptors
Prostatic Neoplasms
Androgens
Neoplasms
Castration
Stomach
Adenocarcinoma
Human Chromosomes
Oncogenes
Renal Cell Carcinoma
Urinary Bladder Neoplasms
Glioma
Disease-Free Survival
Nexus
Hepatocellular Carcinoma
Melanoma
Down-Regulation
Fibroblasts
Epithelial Cells

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Oncology
  • Cancer Research

Cite this

Sakurai, Kohei ; Reon, Brian J. ; Anaya, Jordan ; Dutta, Anindya. / The lncRNA DRAIC/PCAT29 locus constitutes a tumor-suppressive nexus. In: Molecular Cancer Research. 2015 ; Vol. 13, No. 5. pp. 828-838.
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The lncRNA DRAIC/PCAT29 locus constitutes a tumor-suppressive nexus. / Sakurai, Kohei; Reon, Brian J.; Anaya, Jordan; Dutta, Anindya.

In: Molecular Cancer Research, Vol. 13, No. 5, 01.01.2015, p. 828-838.

Research output: Contribution to journalArticle

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