Potential roles of abnormally expressed long noncoding RNA UCA1 and Malat-1 in metastasis of melanoma

Abstract

Melanoma is a highly aggressive skin cancer with increasing incidence worldwide. Long noncoding RNAs (lncRNAs), a group of nonprotein-coding transcripts longer than 200 nucleotides, are pervasively transcribed in the genome and are emerging as new players in tumorigenesis. The primary objective of this study was to investigate the role of six cancer-related lncRNAs in pairs of melanoma and adjacent normal tissues (ANTs). A total of 63 primary melanoma, paired ANTs, and metastatic lesions were collected in a Chinese population. Real-time PCR analysis was carried out to compare a series of cancer-related lncRNAs among primary melanoma tissues, ANTs, and metastatic lesions. In in-vitro studies, transwell migration assay was carried out to estimate the migration abilities of melanoma cells with different expression levels of urothelial carcinoma-associated 1 (UCA1) or metastasis-associated lung adenocarcinoma transcript 1 (Malat-1) lncRNAs. We found that UCA1 and Malat-1 lncRNAs were markedly more increased in melanomas than in paired ANTs (P<0.05). Melanomas at later stages (stages 3-4) showed higher expression of UCA1 lncRNA than those at early stages (stages 1-2) (P=0.455). In melanomas with lymph node metastasis, the metastatic lesions had a relatively higher expression of Malat-1 lncRNA than in paired primary tumors (P=0.414). Knockdown of UCA1 or Malat-1 lncRNA could attenuate the migrational ability of melanoma cells in in-vitro studies. Increased expression of UCA1 and Malat-1 lncRNAs might have a correlation with melanoma metastasis.

Epigenetic regulation in human melanoma: past and future

“…80 Knockdown of HOTAIR inhibited the motility and invasiveness of melanoma cells, with decreased degradation of extracellular matrix. 80 Another study by Tian et al 81 found no statistical difference in expression levels of HOTAIR lncRNA between melanoma and adjacent normal tissue. This observation was attributed to the inclusion criteria of the study that restricted samples only to superficial spreading and nodular melanomas.…”

“…102 MALAT1 is highly expressed in melanoma compared to adjacent normal tissues. 81 Knockdown studies showing an effect of MALAT1 on migration of melanoma cells suggest that MALAT1 may promote melanoma spread as with UCA1. 81 …”

“…101 In a recent study that investigated the roles of 6 cancer-related lncRNAs in paired melanoma and adjacent normal tissues, elevated expression of UCA1 in melanomas was reported, especially at advanced stages. 81 Knockdown of UCA1 suppressed migration of melanoma cells in vitro, suggesting that UCA1 might contribute to tumor dissemination. 81 Functional studies carried out to determine the mechanism of action of this lncRNA have revealed that UCA1 negatively regulates p27 (a tumor suppressor gene) in breast cancer.…”

“…81 Knockdown of UCA1 suppressed migration of melanoma cells in vitro, suggesting that UCA1 might contribute to tumor dissemination. 81 Functional studies carried out to determine the mechanism of action of this lncRNA have revealed that UCA1 negatively regulates p27 (a tumor suppressor gene) in breast cancer. 101 Phosphorylated heterogeneous nuclear ribonucleoprotein 1 (hnRP1) found in cytoplasm forms a complex with UCA1 and increases UCA1 stability.…”

“…This observation was attributed to the inclusion criteria of the study that restricted samples only to superficial spreading and nodular melanomas. 81 HOTAIR recruits PRC2 to specific target genes, leading to H3K27 trimethylation and epigenetic silencing of metastatic suppressor genes. 82 Further mechanistic investigation into the regulation of metastasis by HOTAIR is necessary.…”