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Open Access 01-12-2019 | Melanoma | Research

Downregulation of RNF128 activates Wnt/β-catenin signaling to induce cellular EMT and stemness via CD44 and CTTN ubiquitination in melanoma

Authors: Chuan-Yuan Wei, Meng-Xuan Zhu, Yan-Wen Yang, Peng-Fei Zhang, Xuan Yang, Rui Peng, Chao Gao, Jia-Cheng Lu, Lu Wang, Xin-Yi Deng, Nan-Hang Lu, Fa-Zhi Qi, Jian-Ying Gu

Published in: Journal of Hematology & Oncology | Issue 1/2019

Abstract

Background

Ring finger proteins (RNFs) were involved in carcinogenesis. Here, we aimed to explore the detailed mechanism of RNF128 in the progression of melanoma.

Methods

We reanalyzed several gene expression profiles from the Gene Expression Omnibus (GEO) database and obtained the overlapped differential expressed RNF genes. Among them, RNF128 was selected to further explore its expression, the biological significance, and the underlying molecular mechanism, as well as the clinical relevance in melanoma patients.

Results

RNF128 was found to be significantly downregulated in the selected datasets, which was further verified in our melanoma tissues. Moreover, RNF128 downregulation was shown to correlate with the malignant phenotype of melanoma, and further functional assays demonstrated that low levels of RNF128 promoted melanoma progression via inducing cell epithelial-mesenchymal transition (EMT) and the acquisition of stemness. Mechanistically, RNF128 interference activated the Wnt pathway via simultaneously ubiquitinating CD44/cortactin (CTTN), resulting in CD44 and c-Myc transcription, thus revealed that RNF128 participated in a positive feedback of the Wnt pathway-CD44 loop. Clinically, we found that patients expressing low RNF128 and high CD44/CTTN levels had a poor prognosis.

Conclusion

Downregulated RNF128 activates Wnt signaling to induce cellular EMT and stemness by ubiquitinating and degrading CD44/CTTN, and RNF128 is a reliable diagnostic and prognostic biomarker, and a deeper understanding of RNF128 may contribute to the treatment of melanoma.

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Title: Downregulation of RNF128 activates Wnt/β-catenin signaling to induce cellular EMT and stemness via CD44 and CTTN ubiquitination in melanoma
Authors: Chuan-Yuan Wei
Meng-Xuan Zhu
Yan-Wen Yang
Peng-Fei Zhang
Xuan Yang
Rui Peng
Chao Gao
Jia-Cheng Lu
Lu Wang
Xin-Yi Deng
Nan-Hang Lu
Fa-Zhi Qi
Jian-Ying Gu
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: Melanoma
Melanoma
Published in: Journal of Hematology & Oncology / Issue 1/2019
Electronic ISSN: 1756-8722
DOI: https://doi.org/10.1186/s13045-019-0711-z

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