SOX10 Knockdown Inhibits Melanoma Cell Proliferation via Notch Signaling Pathway

被引:8
作者
Tang, Youqun [1 ]
Cao, Yanming [1 ]
机构
[1] Cent South Univ, Xiangya Hosp 3, Dept Oncol, Changsha 410013, Hunan, Peoples R China
关键词
SOX10; melanoma; bioinformatics; proliferation; biomarkers; CANCER; GENE; HETEROGENEITY; EXPRESSION; PROMOTES;
D O I
10.2147/CMAR.S329331
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: Melanoma is a serious and malignant disease worldwide. Seeking diagnostic markers and potential therapeutic targets is urgent for melanoma treatment. SOX10, a member of the SoxE family of genes, is a transcription factor which can regulate the transcription of a wide variety of genes in multiple cellular processes. Methods: The mRNA level and protein expression of SOX10 is confirmed by bioinfor-matic analysis and IHC staining. MTT, clone formation and EdU analysis showed that SOX10 knockdown (KD) could significantly inhibit melanoma cell proliferation. FACS analysis showed that SOX10 KD could markedly enhance the level of cell apoptosis. The downstream target signaling pathway is predicted by RNA-seq based on the public GEO database. The activation of Notch signaling mediated by SOX10 is tested by qPCR and Western blot. Results: Ectopic upregulation of SOX10 was found in melanoma patient tissues compared to normal nevus tissues in mRNA and protein levels. Furthermore, both mRNA and protein level of SOX10 were negatively correlated with melanoma patient's prognosis. SOX10 knockdown could obviously suppress the proliferation ability of melanoma cells by inacti-vating Notch signaling pathway. Conclusion: Our study confirmed that SOX10 is an oncogene and activate Notch signaling pathway, which suggests the potential treatment for melanoma patients by target SOX10/ Notch axis.
引用
收藏
页码:7225 / 7234
页数:10
相关论文
共 32 条
[1]  
Ayyildiz D, 2019, METHODS MOL BIOL, V1986, P1, DOI 10.1007/978-1-4939-9442-7_1
[2]  
Braune EB, 2016, DISCOV MED, V21, P189
[3]   SOX10 Ablation Arrests Cell Cycle, Induces Senescence, and Suppresses Melanomagenesis [J].
Cronin, Julia C. ;
Watkins-Chow, Dawn E. ;
Incao, Art ;
Hasskamp, Joanne H. ;
Schoenewolf, Nicola ;
Aoude, Lauren G. ;
Hayward, Nicholas K. ;
Bastian, Boris C. ;
Dummer, Reinhard ;
Loftus, Stacie K. ;
Pavan, William J. .
CANCER RESEARCH, 2013, 73 (18) :5709-5718
[4]   Molecular heterogeneity of malignant melanomas [J].
Glatz, K. .
PATHOLOGE, 2007, 28 (06) :474-478
[5]   SOX10 Promotes Melanoma Cell Invasion by Regulating Melanoma Inhibitory Activity [J].
Graf, Saskia A. ;
Busch, Christian ;
Bosserhoff, Anja-Katrin ;
Besch, Robert ;
Berking, Carola .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2014, 134 (08) :2212-2220
[6]   The myelin protein PMP2 is regulated by SOX10 and drives melanoma cell invasion [J].
Graf, Saskia Anna ;
Heppt, Markus Vincent ;
Wessely, Anja ;
Krebs, Stefan ;
Kammerbauer, Claudia ;
Hornig, Eva ;
Strieder, Annamarie ;
Blum, Helmut ;
Bosserhoff, Anja-Katrin ;
Berking, Carola .
PIGMENT CELL & MELANOMA RESEARCH, 2019, 32 (03) :424-434
[7]   Intratumor and Intertumor Heterogeneity in Melanoma [J].
Grzywa, Tomasz M. ;
Paskal, Wiktor ;
Wlodarski, Pawel K. .
TRANSLATIONAL ONCOLOGY, 2017, 10 (06) :956-975
[8]   Sox proteins in melanocyte development and melanoma [J].
Harris, Melissa L. ;
Baxter, Laura L. ;
Loftus, Stacie K. ;
Pavan, William J. .
PIGMENT CELL & MELANOMA RESEARCH, 2010, 23 (04) :496-513
[9]   Mutation of the Sry-related Sox10 gene in Dominant megacolon, a mouse model for human Hirschsprung disease [J].
Herbarth, B ;
Pingault, V ;
Bondurand, N ;
Kuhlbrodt, K ;
Hermans-Borgmeyer, I ;
Puliti, A ;
Lemort, N ;
Goossens, M ;
Wegner, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (09) :5161-5165
[10]   Notch signaling mediates melanoma-endothelial cell communication and melanoma cell migration [J].
Howard, Jason D. ;
Moriarty, Whei F. ;
Park, JinSeok ;
Riedy, Katherine ;
Panova, Izabela P. ;
Chung, Christine H. ;
Suh, Kahp-Yang ;
Levchenko, Andre ;
Alani, Rhoda M. .
PIGMENT CELL & MELANOMA RESEARCH, 2013, 26 (05) :697-707