Objectives: Melanoma is an aggressive skin cancer. Understanding the underlying mechanisms for melanomagenesis and identification of novel and effective melanoma treatment strategies are urgently necessary. The long-noncoding RNAs are considered as new essential players during cancer development, including the melanoma.
Materials and methods: In this study, we first determined the expression of LINC00888 in tumor tissues and adjacent normal tissues from 28 patients with melanoma using quantitative polymerase chain reaction, and the correlation between the expression level of LINC00888 and the survival months was also examined. Next, we investigated the effect of LINC00888 on the proliferation, apoptosis, and invasion in the melanoma cells. Moreover, LINC00888-specific miRNA and target gene were further confirmed using the dual-luciferase reporter assay and Western blotting. Last, the tumorigenesis role of LINC00888 was also explored using tumor xenografts mouse model.
Results: Elevated LINC00888 expression was found in melanoma specimens compared with adjacent normal tissues. The 4-year overall survival in melanoma patients with high expression of LINC00888 was substantially shorter than that in those with low expression of LINC00888. Knockdown of LINC00888 significantly inhibited the proliferation, apoptosis, epithelial-mesenchymal transition, and invasion of melanoma cells, while the overexpression of LINC00888 exerted opposite effect. Furthermore, we revealed that microRNA-126 (miR-126) was able to regulate LINC00888 expression and further influence the expression of CRK. Consistently, miR-126 inhibitor could rescue the expression of CRK in LINC00888-downregulated cells, while miR-126 mimics could reduce the CRK expression level in cells with the overexpression of LINC00888. Last, the animal experiment further demonstrated that the overexpression of LINC00888 enhanced the tumor development in vivo.
Conclusion: Our data showed that long-noncoding RNA LINC00888 functioned as an oncogene in melanoma tumorigenesis, it also regulated the cellular proliferation and invasion of melanoma via miR126/CRK signaling pathway and metastasis via miR-126/CRK signaling axis, which could be a promising molecular target for treating melanoma.
Keywords: apoptosis; long-noncoding RNAs; melanoma; melanomagenesis; proliferation.