RTL1 promotes melanoma proliferation by regulating Wnt/β-catenin signalling

Abstract

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.

Pannexin 1 binds β-catenin to modulate melanoma cell growth and metabolism

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A Six-Gene Signature Predicts Survival of Adenocarcinoma Type of Non-Small-Cell Lung Cancer Patients: A Comprehensive Study Based on Integrated Analysis and Weighted Gene Coexpression Network

“…Infants with severe SGA have abnormal placental DNA methylation of CpG1 in the CG4 region of RTL1, suggesting the existence of disturbed epigenetic control in utero [49]. Overexpression of RTL1 in melanoma cells accelerated cutaneous melanoma cell proliferation, promoted the passage of the cell cycle beyond G1 phase, and increased the expression of cell cycle related genes, and RTL1 promotes melanoma cell proliferation by regulating the Wnt/ β -Catenin signalling pathway [50]. RTL1 activation serves as a driver of HCC.…”

KIF18B promotes tumor progression through activating the Wnt/β-catenin pathway in cervical cancer

“… 35 , 36 In addition, many transcription factor also participate in this regulatory process. 37 – 39 In the present study, we tested the effect of KIF18B knockdown on the Wnt/β-catenin signaling pathway. Compared with the control group, silencing of KIF18B expression decreased the total level of β-catenin, C-myc, and the phosphorylation of GSK3β, but the total level of GSK3β has no obvious differences.…”