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

PLoS One. 2017 Feb 22;12(2):e0172498. doi: 10.1371/journal.pone.0172498. eCollection 2017.

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.

MeSH terms

  • Carcinogenesis / genetics*
  • Carcinogenesis / pathology
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / pathology
  • Databases, Genetic
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Melanoma / genetics*
  • Melanoma / mortality
  • Melanoma / pathology
  • Neoplasm Metastasis / genetics*
  • Neoplasm Metastasis / pathology
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Skin / pathology
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology
  • Survival Rate

Substances

  • RNA, Long Noncoding
  • RNA, Messenger

Grants and funding

This work was financially supported by the National Natural Science Foundation of China (81372369 to HX; 81371661 to PH; and 81101042 to FL) (http://www.nsfc.gov.cn/). As funders, HX, PH, and FL have role in study design and preparation of the manuscript.