Lyn Kinase Promotes the Proliferation of Malignant Melanoma Cells through Inhibition of Apoptosis and Autophagy via the PI3K/Akt Signaling Pathway

Melanoma is characterized by aggressive invasion, early metastasis, and resistance to existing chemotherapeutic agents. Accumulated studies have reported that microRNA (miRNA) is a potentially robust molecular tool for developing future therapeutic technologies. Therefore, examining the expression patterns, biological roles, and associated mechanisms of cancer-related miRNAs in melanoma is essential for developing novel therapeutic targets for patients with this disease. In this study, miRNA-331 (miR-331) was underexpressed in melanoma tissues and cell lines. Functional assays revealed that the enforced expression of miR-331 inhibited cell proliferation and invasion. In addition, astrocyte-elevated gene-1 (AEG-1) was identified as a novel target of miR-331 through bioinformatics analysis, reverse transcription quantitative polymerase chain reaction analysis, Western blot analysis, dual-luciferase reporter assay, and Spearman’s correlation analysis. Furthermore, reintroduction of AEG-1 partially abrogated the inhibitory effects of miR-331 overexpression on the proliferation and invasion of melanoma cells. Moreover, miR-331 suppressed the activation of the PTEN/AKT signaling pathway in melanoma by inhibiting AEG-1. In short, miR-331 may play tumor-suppressive roles in melanoma by directly targeting AEG-1 and regulating the PTEN/AKT signaling pathway, suggesting that miR-331 could be investigated as a therapeutic strategy for patients with this malignancy.

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Dual VEGF/PDGF knockdown suppresses vasculogenic mimicry formation in choroidal melanoma cells via the Wnt5a/β-catenin/AKT signaling pathway

Acta Histochemica ◽

10.1016/j.acthis.2021.151842 ◽

2022 ◽

Vol 124 (1) ◽

pp. 151842

Author(s):

Yingying Yuan ◽

Bochao Geng ◽

Xiaoyan Xu ◽

Han Zhao ◽

Jingyi Bai ◽

...

Keyword(s):

Signaling Pathway ◽

Vasculogenic Mimicry ◽

Choroidal Melanoma ◽

Melanoma Cells ◽

Akt Signaling ◽

Akt Signaling Pathway

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Ailanthone Induces Cell Cycle Arrest and Apoptosis in Melanoma B16 and A375 Cells

Biomolecules ◽

10.3390/biom9070275 ◽

2019 ◽

Vol 9 (7) ◽

pp. 275 ◽

Cited By ~ 5

Author(s):

Wenjing Liu ◽

Xiaona Liu ◽

Zhaohai Pan ◽

Dan Wang ◽

Minjing Li ◽

...

Keyword(s):

Cell Cycle ◽

Malignant Melanoma ◽

Cell Cycle Arrest ◽

Signaling Pathway ◽

Cell Apoptosis ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Melanoma B16 ◽

Cycle Arrest ◽

A375 Cells

Malignant melanoma is the most lethal type of skin cancer. Previous studies have shown that ailanthone has potent antitumor activity in a variety of cell lines. However, the anti-tumor effect of ailanthone on malignant melanoma remains unclear. To investigate the anti-tumor mechanisms of ailanthone in human melanoma B16 and mouse melanoma A375 cells, the cell counting kit-8 assay, colony formation assay, DNA content analysis, Hoechst 33258, and Annexin V-FITC/PI staining were used to assess cell proliferation, cell cycle distribution, and cell apoptosis, respectively. Western blotting was performed to evaluate the expression of cell cycle- and apoptosis-related proteins and regulatory molecules. The results showed that ailanthone significantly inhibited melanoma B16 and A375 cell proliferation as well as remarkably induced cell cycle arrest at the G0–G1 phase in B16 cells and the G2–M phase in A375 cells in a dose-dependent manner. Further investigation revealed that ailanthone promoted the expression of p21 and suppressed the expression of cyclin E in B16 cells or cyclin B in A375 cells through the PI3K-Akt signaling pathway. In addition, ailanthone induced B16 and A375 cell apoptosis via a caspase-dependent mechanism. Further studies showed that ailanthone remarkably downregulated Bcl-2 and upregulated Apaf-1 and Bax, and subsequently increased mitochondrial membrane permeabilization and released cytochrome c from the mitochondria in B16 cells and A375 cells. Taken together, ailanthone induces cell cycle arrest via the PI3K-Akt signaling pathway as well as cell apoptosis via the mitochondria-mediated apoptotic signaling pathway. Ailanthone may be potentially utilized as an anti-tumor agent in the management of malignant melanoma.

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