Long non-coding RNA CASC15 promotes melanoma progression by epigenetically regulating PDCD4

Abstract

BackgroundLong non-coding RNAs (LncRNAs) have been identified as critical regulators in a variety of cancer types. Cancer susceptibility candidate 15 (CASC15), a lncRNA located at chromosome 6p22.3, has been discovered to participate in melanoma progression and phenotype switching. Nevertheless, the roles and molecular mechanisms of CASC15 in melanoma are far from being understood.ResultsWe found that CASC15 expression was up-regulated in melanoma tissues and associated with advanced pathological stages. Function experiments displayed that CASC15 knockdown hindered proliferation, facilitated apoptosis and suppressed invasion, while CASC15 overexpression facilitated proliferation and invasion in melanoma cells. Further mechanistic analysis showed that CASC15 epigenetically silenced the expression of programmed cell death 4 (PDCD4) by recruiting EZH2 and increasing H3K27me3 level at the promoter region of PDCD4. Additionally, PDCD4 overexpression inhibited proliferation, enhanced apoptosis and decreased invasion of melanoma cells. Moreover, CASC15-knockdown-induced anti-cancer effects were abated by PDCD4 down-regulation. Furthermore, depletion of CASC15 blocked tumor growth of melanoma by up-regulating PDCD4 in vivo.ConclusionsCASC15 acts as an oncogene by negatively regulating PDCD4 expression via recruiting EZH2 and subsequently increasing H3K27me3 level. Together, our study indicates that CASC15/EZH2/PDCD4 may serve as a promising therapeutic target for melanoma intervention.

<p>Long non-coding RNA LINC00662 promotes proliferation and migration in oral squamous cell carcinoma</p>

“…Emerging researches have reported that large number of lncRNAs are deregulated in human cancers 18–20. These differentially expressed lncRNAs are closely contributed to tumor growth, metastasis, apoptosis or diagnosis, acting as antioncogenes or oncogenes 21–23. In addition, LINC00662 was significantly upregulated in lung squamous carcinoma compared with lung adenocarcinoma,12 and increased in nasopharyngeal carcinoma 14.…”

Long noncoding RNA OIP5‐AS1 aggravates cell proliferation, migration in gastric cancer by epigenetically silencing NLRP6 expression via binding EZH2

“…29 For instance, the broad tendency of lncRNAs existing in nucleus is to interact with genomic DNA, transcription factors, spliceosomes, chromatin regulators, and so on, implicating in transcriptional and epigenetic regulations containing histone modifications. 30 Regulatory ncRNAs such as PCAT6, 31 LINC00968, 32 TUG1, 33 and CASC15 34 were reported to interact with EZH2, increasing F I G U R E 3 OIP5-AS1 represses NLRP6 expression by recruiting EZH2, increasing the H3K27me3 enrichment of NLRP6 promoter. A, qRT-PCR assay interrogated EZH2 mRNA level after transfection of pcDNA3.1 or pcDNA3.1/EZH2 into AGS and SGC7901 cells.…”

TUG1 confers cisplatin resistance in esophageal squamous cell carcinoma by epigenetically suppressing PDCD4 expression via EZH2

“…EZH2, a vital catalytic subunit of PRC2, is a histone methyltransferase that epigenetically represses gene expression by promoting histone H3 lysine 27 trimethylation (H3 K27me3) [ 28 , 29 ]. PDCD4, a tumor suppressor, was recently demonstrated to be negatively regulated by CASC15, via recruiting EZH2 and subsequently changing H3 K27me3 level in melanoma [ 30 ]. Therefore, we further investigated whether TUG1 could regulate PDCD4 expression by recruiting EZH2.…”