Characterization of long noncoding RNA and messenger RNA signatures in melanoma tumorigenesis and metastasis

Abstract

The incidence of melanoma, the most aggressive and life-threatening form of skin cancer, has significantly risen over recent decades. Therefore, it is essential to identify the mechanisms that underlie melanoma tumorigenesis and metastasis and to explore novel and effective melanoma treatment strategies. Accumulating evidence s uggests that aberrantly expressed long noncoding RNAs (lncRNAs) have vital functions in multiple cancers. However, lncRNA functions in melanoma tumorigenesis and metastasis remain unclear. In this study, we investigated lncRNA and messenger RNA (mRNA) expression profiles in primary melanomas, metastatic melanomas and normal skin samples from the Gene Expression Omnibus database. We used GSE15605 as the training set (n = 74) and GSE7553 as the validation set (n = 58). In three comparisons (primary melanoma versus normal skin, metastatic melanoma versus normal skin, and metastatic melanoma versus primary melanoma), 178, 295 and 48 lncRNAs and 847, 1758, and 295 mRNAs were aberrantly expressed, respectively. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses to examine the differentially expressed mRNAs, and potential core lncRNAs were predicted by lncRNA-mRNA co-expression networks. Based on our results, 15 lncRNAs and 144 mRNAs were significantly associated with melanoma tumorigenesis and metastasis. A subsequent analysis suggested a critical role for a five-lncRNA signature during melanoma tumorigenesis and metastasis. Low expression of U47924.27 was significantly associated with decreased survival of patients with melanoma. To the best of our knowledge, this study is the first to explore the expression patterns of lncRNAs and mRNAs during melanoma tumorigenesis and metastasis by re-annotating microarray data from the Gene Expression Omnibus (GEO) microarray dataset. These findings reveal potential roles for lncRNAs during melanoma tumorigenesis and metastasis and provide a rich candidate reservoir for future studies.

Long non‐coding RNA lnc‐PCTST predicts prognosis through inhibiting progression of pancreatic cancer by downregulation of TACC‐3

“…Due to nonspecific symptoms, most PC patients are diagnosed with advanced and distant metastasis. Recent study has revealed lncRNAs are essential for tumorigenesis of cancer; [27][28][29][30] nevertheless, the specific mechanisms still remain unclear and require further investigation. 26 Therefore, it is of extreme importance to identify the mechanisms of tumorigenesis and metastasis, thus improving overall survival in PC patients.…”

“…26 Therefore, it is of extreme importance to identify the mechanisms of tumorigenesis and metastasis, thus improving overall survival in PC patients. Recent study has revealed lncRNAs are essential for tumorigenesis of cancer; [27][28][29][30] nevertheless, the specific mechanisms still remain unclear and require further investigation.…”

Increased expression of long noncoding RNA GAS6‐AS2 promotes proliferation and inhibits apoptosis of melanoma cells via upregulating GAS6 expression

“…To date, studies on molecular mechanisms of melanoma mainly focus on protein‐coding genes, such as NRAS , MTOR , CDKN2A , and BRAF . However, the initiation and progression of melanoma could not be fully explained by protein‐coding genes . High‐throughput transcriptome sequencings have identified tens of thousands of noncoding RNAs, many of which have important roles in biology .…”

“…[6][7][8] However, the initiation and progression of melanoma could not be fully explained by protein-coding genes. 9,10 High-throughput transcriptome sequencings have identified tens of thousands of noncoding RNAs, many of which have important roles in biology. 11,12 Long noncoding RNA (lncRNA), which represents a large group of noncoding RNAs, is defined as one with more than 200 nucleotides in length.…”

Melanoma from Molecular Pathways to Clinical Treatment: An Up to Date Review

“…It has been observed that acquired resistance to BRAF inhibitors is usually characterized by reactivation of the MAPK pathway [16]. There are post-transcriptional adaptive changes which induce the development of drug resistance, these are mostly mechanisms involving non-coding RNAs [17]. In the current mini review we will include the most important molecular pathways and up-to-date treatment modalities in short.…”