Abstract
Melanoma is a disease with a high recurrence rate and poor prognosis; therefore, the need for targeted therapeutics is steadily increasing. Oligodendrocyte transcription factor2 (Olig2) is a basic helix-loop-helix transcription factor that is expressed in the central nervous system during embryonic development. Olig2 is overexpressed in various malignant cell lines such as lung carcinoma, glioma and melanoma. Olig2 is known as a key transcription factor that promotes tumor growth in malignant glioma. However, the role of Olig2 in melanoma is not well characterized. We analyzed the role of Olig2 in apoptosis, migration, and invasion of melanoma cells. We confirmed that Olig2 was overexpressed in melanoma cells and tissues. Reduction of Olig2 increased apoptosis in melanoma cells by increasing p53 level and caspase-3/-7 enzyme activity. In addition, downregulation of Olig2 suppressed migration and invasion of melanoma cells by inhibiting EMT. Reduction of Olig2 inhibited expression of MMP-1 and the enzyme activity of MMP-2/-9 induced by TGF-β. Moreover, Olig2 was involved in the downstream stages of MEK/ERK and PI3K/AKT, which are major signaling pathways in metastatic progression of melanoma. In conclusion, this study demonstrated the crucial roles of Olig2 in apoptosis, migration, and invasion of melanoma and may help to further our understanding of the relationship between Olig2 and melanoma progression.
Highlights
Melanoma is a disease with a high recurrence rate and poor prognosis; the need for targeted therapeutics is steadily increasing
To examine the basal expression of Olig[2], we performed immunoblotting in normal human epidermal melanocytes (NHEM) and four human metastatic melanoma cell lines (MNT-1, 501mel, A375, and HM3KO)
Olig[2] was expressed significantly higher in the four metastatic melanoma cell lines compared with NHEM
Summary
Melanoma is a disease with a high recurrence rate and poor prognosis; the need for targeted therapeutics is steadily increasing. We analyzed the role of Olig[2] in apoptosis, migration, and invasion of melanoma cells. This study demonstrated the crucial roles of Olig[2] in apoptosis, migration, and invasion of melanoma and may help to further our understanding of the relationship between Olig[2] and melanoma progression. When cytochrome c is released into the cytoplasm through the mitochondrial pore, the apoptotic protease activation factor-1 (Apaf-1)/ cytochrome c complex (called the apoptosome) is formed. Olig[2] was thought to be expressed only in neural tissue, Ying-Wei Lin et al found that it is expressed in various tissues including kidney, thymus, lung, brain, and skin They found overexpression of Olig[2] in malignant cell lines from lung carcinoma, breast cancer, and melanoma[20]. We show that Olig[2] is highly expressed in various melanoma cell lines and contributes to invasive growth of melanoma cells
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