Overexpressed VEPH1 inhibits epithelial-mesenchymal transition, invasion, and migration of human cutaneous melanoma cells through inactivating the TGF-β signaling pathway

• Published in: Cell cycle (Georgetown, Tex.) Vol. 18; no. 21; pp. 2860 - 2875
• Main Authors: Feng, Hao, Jia, Xiao-Min, Gao, Ni-Na, Tang, Hua, Huang, Wei, Ning, Ning
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 02.11.2019
• Subjects: Adult; Aged; Animals; Apoptosis - physiology; Benzamides - pharmacology; Cadherins - biosynthesis; Cell Line, Tumor; Cell Movement - physiology; Cell Proliferation - physiology; Dioxoles - pharmacology; Epithelial-Mesenchymal Transition - physiology; Female; Humans; Intracellular Signaling Peptides and Proteins - biosynthesis; Intracellular Signaling Peptides and Proteins - metabolism; Male; Melanoma - pathology; Mice; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Neoplasm Invasiveness - pathology; Prognosis; Research Paper; Signal Transduction - physiology; Skin Neoplasms - pathology; Smad4 Protein - biosynthesis; Transforming Growth Factor beta1 - antagonists & inhibitors; Vimentin - biosynthesis; migration; epithelial-mesenchymal transition; TGF-β signaling pathway; invasion; human cutaneous melanoma; VEPH1
• ISSN: 1538-4101; 1551-4005
• DOI: 10.1080/15384101.2019.1638191

Malignant melanoma has a profound influence on populations around the world, with the underlying mechanisms controlling this disease yet to be fully identified. Hence, the current study aimed to investigate effects associated with VEPH1 on epithelial-mesenchymal transition (EMT), proliferation, invasion, migration and the apoptosis of human cutaneous melanoma (CM) cells through the TGF-β signaling pathway. Microarray-based gene analysis was initially performed to screen the CM-related differentially expressed genes. The expression of VEPH1, TGF-β signaling pathway- and EMT-related genes in CM tissues and cell lines was subsequently evaluated. Gain-of- and loss-of-function experiments were conducted to examine the effects of VEPH1 and the TGF-β signaling pathway on the expression of EMT-related genes, cell proliferation, migration, invasion, cell cycle and apoptosis . Finally, tumor formation in nude mice was conducted. VEPH1 was lowly expressed and regulated the progression of CM with involvement in the TGF-β signaling pathway. Human CM tissues were noted to activate the TGF-β signaling pathway and EMT. A375 cells treated with overexpressed VEPH1 plasmids or/and TGF-β signaling pathway inhibitor SB-431542 displayed diminished TGF-β, SMAD4, Vimentin and N-cadherin expression while the expression of E-cadherin was elevated, accompanied by decreased cell proliferation, migration, invasion, inhibited cell cycle entry. However, si-VEPH1 or TGF-β signaling pathway activator contributed to reverse results. Taken together, the key findings of the current study present evidence suggesting that VEPH1 protects against human CM by inhibiting the activation of the TGF-β signaling pathway, highlighting its potential as a target for the prognosis and diagnosis of CM.