Characterization of long noncoding RNA and messenger RNA signatures in melanoma tumorigenesis and metastasis.
Characterization of long noncoding RNA and messenger RNA signatures in melanoma tumorigenesis and metastasis.
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黑色素瘤肿瘤发生和转移中长非编码 RNA 和信使 RNA 特征的表征
DOI：
10.1371/journal.pone.0172498
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Han P
中科院分区：
文献类型：
--
作者：
Wang S;Fan W;Wan B;Tu M;Jin F;Liu F;Xu H;Han P
黑色素瘤是最具侵袭性和威胁生命的皮肤癌，其发病率在近几十年来显著上升。因此，必须确定黑色素瘤肿瘤发生和转移的机制，并探索新的和有效的黑色素瘤治疗策略。越来越多的证据表明，异常表达的长链非编码RNA（lncRNA）在多种肿瘤中发挥重要作用。然而，lncRNA在黑色素瘤肿瘤发生和转移中的功能仍不清楚。在这项研究中，我们调查lncRNA和信使RNA（mRNA）的表达谱在原发性黑色素瘤，转移性黑色素瘤和正常皮肤样本的基因表达综合数据库。我们使用GSE 15605作为训练集（n = 74），GSE 7553作为验证集（n = 58）。在三个比较中（原发性黑素瘤与正常皮肤，转移性黑素瘤与正常皮肤，以及转移性黑素瘤与原发性黑素瘤），分别有178、295和48个lncRNA和847、1758和295个mRNA异常表达。我们进行了基因本体论和京都基因百科全书和基因组通路分析，以检查差异表达的mRNA，并通过lncRNA-mRNA共表达网络预测潜在的核心lncRNA。根据我们的研究结果，15个lncRNA和144个mRNA与黑色素瘤的发生和转移显著相关。随后的分析表明，在黑色素瘤肿瘤发生和转移过程中，5-lncRNA签名起着关键作用。U47924.27的低表达与黑色素瘤患者的生存率降低显著相关。据我们所知，这项研究是第一个探索在黑色素瘤肿瘤发生和转移过程中的lncRNA和mRNA的表达模式，通过重新注释基因表达综合（GEO）微阵列数据集的微阵列数据。这些发现揭示了lncRNA在黑色素瘤发生和转移过程中的潜在作用，并为未来的研究提供了丰富的候选库。
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.