Upregulation of UHRF1 promotes the progression of melanoma by inducing cell proliferation

Wei, Chuan‐Yuan; Lu, Nan‐Han; Wang, Lu; Zhang, Yong; Yang, Yanwen; Qi, Fazhi; Gu, Jiande

doi:10.3892/or.2018.6356

Cited by 21 publications

(22 citation statements)

References 40 publications

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“…The primer sequences for qRT-PCR are shown in Additional file 2: Table S1. Western blot was performed as described in a previous study [15], and all the primary antibodies are listed in Additional file 1: Table S2.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2019

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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. Electronic supplementary material The online version of this article (10.1186/s13045-019-0711-z) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

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

et al. 2019

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“…IHC was performed as previously described [20]. Briefly, the slides were deparaffinised in xylene and rehydrated in graded ethanol.…”

Section: Methodsmentioning

confidence: 99%

TRIM44 activates the AKT/mTOR signal pathway to induce melanoma progression by stabilizing TLR4

Wei

Wang

Zhu

et al. 2019

J Exp Clin Cancer Res

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Background There is growing evidence that tripartite motif-containing protein 44 (TRIM44) plays crucial role in tumor development. However, the underlying mechanism of this deubiquitinating enzyme remains unclear. Methods Large clinical samples were used to detect TRIM44 expression and its associations with clinicopathological features and prognosis. Gain- and loss-of-function experiments in cell lines and mouse xenograft models were performed to elucidate the function and underlying mechanisms of TRIM44 induced tumor progression. Co-immunoprecipitation (Co-IP) assays and mass spectrometric analyses were applied to verify the interacting proteins of TRIM44. Results We found that TRIM44 was commonly amplified in melanoma tissues compared with paratumoral tissues. TRIM44 expression also positively correlated with more aggressive clinicopathological features, such as Breslow depth ( p = 0.025), distant metastasis ( p = 0.012), and TNM stage ( p = 0.002). Importantly, we found that TRIM44 was an independent indicator of prognosis for melanoma patients. Functionally, overexpression of TRIM44 facilitated cell invasion, migration, apoptosis resistance and proliferation in vitro, and promoted lung metastasis and tumorigenic ability in vivo. Importantly, high level of TRIM44 induced melanoma cell epithelial-mesenchymal transition (EMT), which is one of the most important mechanisms for the promotion of tumor metastasis. Mechanistically, high levels of TRIM44 increased the levels of p-AKT (T308) and p-mTOR (S2448), and a specific AKT inhibitor inhibited TRIM44-induced tumor progression. Co-IP assays and mass spectrometric analyses indicated that TRIM44 overexpression induces cell EMT through activating AKT/mTOR pathway via directly binding and stabilizing TOLL-like receptor 4 (TLR4), and TLR4 interference impeded TRIM44 induced tumor progression. Moreover, we demonstrated that TRIM44 is the target of miR-26b-5p, which is significantly downregulated in melanoma tissues and may be responsible for the overexpression of TRIM44. Conclusions TRIM44, regulated by miR-26b-5p, promotes melanoma progression by stabilizing TLR4, which then activates the AKT/mTOR pathway. TRIM44 shows promise as a prognostic predictor and a therapeutic target for melanoma patients. Electronic supplementary material The online version of this article (10.1186/s13046-019-1138-7) contains supplementary material, which is available to authorized users.

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“…Western blotting was performed as in a previous study 17. Briefly, cells were lysed with RIPA buffer (Beyotime, Shanghai, China) containing phosphatase inhibitor cocktail.…”

Section: Methodsmentioning

confidence: 99%

<p>Elevated nuclear auto-antigenic sperm protein promotes melanoma progression by inducing cell proliferation</p>

Wei

Cao

et al. 2019

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BackgroundNuclear auto-antigenic sperm protein (NASP) has been implicated in tumorigenesis. However, its role in melanoma is still unclear.Materials and methodsIn the present study, we detected the mRNA and protein level of NASP in melanoma cell lines and tissues. Then the role of NASP was investigated by transfecting with NASP siRNAs. Finally, the prognosis of NASP was analyzed in 100 melanoma patients through Cox regression and Kaplan–Meier analyses.ResultsWe showed that NASP was significantly overexpressed in melanoma tissues, and unregulated NASP promoted melanoma cell proliferation via promoting cell cycle G1/S phase transition. Additionally, the expression of NASP was closely related to proliferating cell nuclear antigen, a widely accepted biomarker for cell proliferation. Clinically, we found that a high level of NASP predicated poor overall survival and high cumulative recurrence rates. Multivariate analysis revealed that NASP was a risk biomarker for predicting the prognosis of melanoma patients.ConclusionElevated NASP plays an important role in melanoma cell proliferation and tumor progression, and it can be used as an independent prognostic biomarker for melanoma patients.

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Upregulation of UHRF1 promotes the progression of melanoma by inducing cell proliferation

Cited by 21 publications

References 40 publications

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

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

TRIM44 activates the AKT/mTOR signal pathway to induce melanoma progression by stabilizing TLR4

<p>Elevated nuclear auto-antigenic sperm protein promotes melanoma progression by inducing cell proliferation</p>

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