Melanoma is the most malignant cutaneous cancer and causes over 9000 deaths annually. Because fatality rates from malignant melanoma (MM) increase dramatically upon metastasis, we investigated tumorigenesis and metastasis of MM in transcriptome analyses of three distinct cell lines that correspond with the stages of MM pathogenesis: the normal stage (HEMn-LP), the onset of MM (A375), and the metastasis stage (A2058). Using next-generation sequencing (NGS) technology, we detected asymmetrical expression of genes among the three cell lines, notably on chromosomes 9, 11, 12, and 14, suggesting their involvement in tumorigenesis and metastasis of MM. These genes were clustered into 41 categories based on their expression patterns, and their biological functions were analyzed using Ingenuity Pathway Analysis. In the top cancer-associated category, HIF1A, IL8, TERT, ONECUT1, and FOXA1 directly interacted with either transcription factors or cytokines that are known to be involved in the tumorigenesis or metastasis of other malignant tumors. The present data suggest that cytokine regulatory pathways in macrophages predominate over other pathways during the pathogenesis of MM. This study provides new targets for the downstream mechanistic studies of the tumorigenesis and metastasis of MM and demonstrates a new strategy for studies of the progression of other malignant cancers.
Bibliographical noteFunding Information:
The authors thank Drs. Yu Li and Jiewu Liu for critically reading the manuscript. This research was supported by the “Strategic Priority Research Program” of the Chinese Academy of Sciences, Stem Cell and Regenerative Medicine Research ( XDA01040405 to X.F.), National Programs for High Technology Research and Development (863 Projects, 2012AA022502 to X.F.), National Key Scientific Instrument and Equipment Development Projects of China ( 2011YQ03013404 to X.F.), Chinese Academy of Sciences Visiting Professorship for Senior International Scientists ( 2010T2S20 ), and the High-end Foreign Experts Talents Program ( GDJ20120491014 ) to E.K.W.
- Next-generation sequencing
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