RTL1 promotes melanoma proliferation by regulating Wnt/β-catenin signalling
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Guobiao Fan1,2, Dan Ye1, Songcheng Zhu1, Jiajie Xi1, Xudong Guo1, Jing Qiao1, Yukang Wu1, Wenwen Jia1, Guiying Wang1, Guohuang Fan1 and Jiuhong Kang1
1Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signalling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Science and Technology, Tongji University, Shanghai 200092, China
2Skin and Cosmetic Research Department, Shanghai Skin Disease Hospital, Tongji University, Shanghai 200443, China
Jiuhong Kang, email: [email protected]
Guiying Wang, email: [email protected]
Guohuang Fan, email: [email protected]
Keywords: melanoma; proliferation; retrotransposon-like 1; β-Catenin; Wnt signalling
Received: July 05, 2017 Accepted: October 30, 2017 Published: November 20, 2017
Cutaneous melanoma is a highly malignant and metastatic skin cancer with high mortality. However, its underlying mechanisms remain largely unclear. Here, we found that retrotransposon-like 1 (RTL1) is highly enriched in melanoma tissue, especially in early and horizontal growth tissues. Knockdown of RTL1 in melanoma cells resulted in cell proliferation suppression; cell cycle arrest at G1 phase; and down-regulation of E2F1, CYCLIN D1, cyclin-dependent kinase 6 (CDK6) and c-MYC. Moreover, overexpression of RTL1 in melanoma cells accelerated cell proliferation, promoted passage of the cell cycle beyond G1 phase, and increased the expression of cell cycle related genes. Mechanistically, we found that knockdown of RTL1 inhibited the Wnt/β-Catenin pathway by regulating the expression of genes specifically involved in β-CATENIN stabilization. Furthermore, the overexpression and knockdown of β-CATENIN rescued the effects of RTL1 on melanoma cell proliferation and the cell cycle. These findings were also confirmed via tumour xenografts in nude mice. Together, our results demonstrated that RTL1 promotes melanoma cell proliferation by regulating the Wnt/β-Catenin signalling pathway.
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