Department of Genetic Engineering and Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin, 17104, Republic of Korea.
Natural Products Research Institute, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea.
Sci Rep. 2021 Apr 8;11(1):7778. doi: 10.1038/s41598-021-87438-x.
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.
黑色素瘤是一种复发率高、预后差的疾病;因此,对靶向治疗的需求正在稳步增加。少突胶质细胞转录因子 2(Olig2)是一种基本螺旋-环-螺旋转录因子,在胚胎发育过程中表达于中枢神经系统。Olig2 在各种恶性细胞系中过度表达,如肺癌、神经胶质瘤和黑色素瘤。Olig2 被认为是促进恶性神经胶质瘤肿瘤生长的关键转录因子。然而,Olig2 在黑色素瘤中的作用尚未得到很好的描述。我们分析了 Olig2 在黑色素瘤细胞凋亡、迁移和侵袭中的作用。我们证实 Olig2 在黑色素瘤细胞和组织中过度表达。通过增加 p53 水平和 caspase-3/-7 酶活性,降低 Olig2 的表达可增加黑色素瘤细胞的凋亡。此外,下调 Olig2 通过抑制 EMT 抑制黑色素瘤细胞的迁移和侵袭。降低 Olig2 抑制了 TGF-β诱导的 MMP-1 和 MMP-2/-9 的酶活性。此外,Olig2 参与了 MEK/ERK 和 PI3K/AKT 的下游阶段,这是黑色素瘤转移进展的主要信号通路。总之,本研究表明 Olig2 在黑色素瘤细胞凋亡、迁移和侵袭中起着至关重要的作用,可能有助于进一步了解 Olig2 与黑色素瘤进展之间的关系。