The CASC15 Long Intergenic Noncoding RNA Locus Is Involved in Melanoma Progression and Phenotype Switching

Laurent Lessard, Michelle Liu, Diego M. Marzese, Hongwei Wang, Kelly Chong, Neal Kawas, Nicholas C. Donovan, Eiji Kiyohara, Sandy Hsu, Nellie Nelson, Sivan Izraely, Orit Sagi-Assif, Isaac P. Witz, Xiao Jun Ma, Yuling Luo, Dave S.B. Hoon*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

Abstract

In recent years, considerable advances have been made in the characterization of protein-coding alterations involved in the pathogenesis of melanoma. However, despite their growing implication in cancer, little is known about the role of long noncoding RNAs in melanoma progression. We hypothesized that copy number alterations (CNAs) of intergenic nonprotein-coding domains could help identify long intergenic noncoding RNAs (lincRNAs) associated with metastatic cutaneous melanoma. Among several candidates, our approach uncovered the chromosome 6p22.3 CASC15 (cancer susceptibility candidate 15) lincRNA locus as a frequently gained genomic segment in metastatic melanoma tumors and cell lines. The locus was actively transcribed in metastatic melanoma cells, and upregulation of CASC15 expression was associated with metastatic progression to brain metastasis in a mouse xenograft model. In clinical specimens, CASC15 levels increased during melanoma progression and were independent predictors of disease recurrence in a cohort of 141 patients with AJCC (American Joint Committee on Cancer) stage III lymph node metastasis. Moreover, small interfering RNA (siRNA) knockdown experiments revealed that CASC15 regulates melanoma cell phenotype switching between proliferative and invasive states. Accordingly, CASC15 levels correlated with known gene signatures corresponding to melanoma proliferative and invasive phenotypes. These findings support a key role for CASC15 in metastatic melanoma.

Original languageEnglish
Pages (from-to)2464-2474
Number of pages11
JournalJournal of Investigative Dermatology
Volume135
Issue number10
DOIs
StatePublished - 14 Oct 2015

Funding

FundersFunder number
National Institutes of Health
National Cancer InstituteR01CA167967, P01CA029605
Dr. Miriam and Sheldon G. Adelson Medical Research Foundation1R01CA167967-01A1, PO1 CA029605

    Fingerprint

    Dive into the research topics of 'The CASC15 Long Intergenic Noncoding RNA Locus Is Involved in Melanoma Progression and Phenotype Switching'. Together they form a unique fingerprint.

    Cite this