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

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 non-coding RNAs in melanoma progression. We hypothesized that copy number alterations of intergenic non-protein coding domains could help identify long intergenic non-coding RNAs (lincRNAs) associated with metastatic cutaneous melanoma. Among several candidates, our approach uncovered the chromosome 6p22.3 CASC15 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 up-regulation 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 stage III lymph node metastasis. Moreover, 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.

Evaluation of GWAS-identified SNPs at 6p22 with neuroblastoma susceptibility in a Chinese population

“…The FLJ22536 gene on 6p22 is also known as cancer susceptibility candidate 15 (CASC15) or LINC00340 [12]; it has many predicted isoforms as well as potential epidermal growth factor-like domain [8]. In mouse xenograft model, high expression of CASC15 was associated with metastatic progression [18], while low expression of shortened CASC15 isoform was associated with advanced neuroblastoma and poor survival for neuroblastoma patients [19]. Attenuating of CASC15 isoform may increase cellular growth and migratory capacity for human neuroblastoma cells which indicated the CASC15 isoform as a mediator of neural growth and differentiation [19].…”

Potential of long non‐coding RNAs in cancer patients: From biomarkers to therapeutic targets

“…While lnc‐BCL2L11‐3 was significantly increased in the recurrent nasopharyngeal carcinoma (NPC), a reduction in lnc‐AL355149.1–1 and lnc‐ZNF674‐1 expression could be a predictor of NPC recurrence . Other lncRNAs known to possess predictive potential for tumor recurrence include lnc‐MX1‐1 for prostate cancer; CASC15 for melanoma; PRINS for adrenocortical carcinoma; and ASLNC22381 and ASLNC20819 for glioblastoma . An integrated mRNA (FCGR1A, RSAD2, CHRDL1) and lncRNA (HIF1A‐AS2, AK124454) signature could also predict the recurrence‐free survival of triple negative breast cancer patients …”

Oncogenic RAS Regulates Long Noncoding RNA Orilnc1 in Human Cancer

“…For example, SPRY4-IT1 (31, 32), BANCR (33), DRAIC/PCAT29 (34), CASC15 (35), MIR31HG (36), SPRIGHTLY (37), RMEL3 (38), SLNCR1 (39) and SAMMSON (40) have been proposed to serve as novel oncogenes or tumor suppressor genes in melanoma. The discovery of lncRNA cancer driver will contribute to cancer diagnosis and treatment.…”