Germline determinants of clinical outcome of cutaneous melanoma

Vogelsang, Matjaž; Wilson, Mathew; Kirchhoff, Tomas

doi:10.1111/pcmr.12418

Cited by 12 publications

(11 citation statements)

References 90 publications

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“… 1 Despite exhibiting a relatively steady increase in its prevalence, melanoma mortality rates have not displayed any increased in recent years for a number of reasons, including continuous incremental advances made in the early diagnostic modalities associated with the condition. 2 Melanoma is accompanied by poor prognoses with a median stage IV survival time ranging between 8 and 18 months postdiagnosis. 3 Melanoma is rarely observed among children, with children accounting for approximately 3% of all pediatric malignancies and <1% of all melanomas worldwide.…”

Section: Introductionmentioning

confidence: 99%

RETRACTION: Mechanism of MicroRNA-708 Targeting BAMBI in Cell Proliferation, Migration, and Apoptosis in Mice With Melanoma via the Wnt and TGF-β Signaling Pathways

Yan

Jin

et al. 2018

Technol Cancer Res Treat

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Objective:The aim of this study was to evaluate the mechanisms involved with miRNA-708 and its targeting of bone morphogenetic protein and activin membrane-bound inhibitor in cell proliferation, migration, and apoptosis in mice with melanoma via the Wnt and transforming growth factor β signaling pathways.Methods:Sixty mice were recruited of which 40 were subsequently assigned into the experimental group (22 mice were successfully established as melanoma model and 18 mice used in tumor xenograft), and the normal control group consisted of 20 mice. B16 cells were assigned to the normal, blank, and negative control, miR-708 mimics, miR-708 inhibitors, si-BAMBI, and miR-708 inhibitors + si-bone morphogenetic protein and activin membrane-bound inhibitor groups. Western blotting and reverse transcription quantitative polymerase chain reaction were employed to detect the expression levels within the tissues and cell lines. TCF luciferase reporter (TOP-FLASH) or a control vector (FOP-FLASH) was applied to detect the activity of the Wnt signaling pathway. MTT3-(4,5-Dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay, flow cytometry, scratch test, and Transwell assay were conducted, respectively, for cell proliferation, apoptosis, migration, and invasion, while tumor xenograft procedures were performed on the nude mice recruited for the study.Results:Compared to the normal control group, the model group displayed increased expressions of bone morphogenetic protein and activin membrane-bound inhibitor, Wnt10B, P53, and Bcl-2; TOPflash activity; β-catenin expression; cell proliferation; migration; and invasion capabilities while decreased expressions of miR-708, vascular endothelial growth factor, Fas, Bax, Caspase-3, and cleaved Caspase-3 and apoptosis rate. Compared to the blank and negative control groups, the miR-708 mimics and small-interfering RNA-bone morphogenetic protein and activin membrane-bound inhibitor groups exhibited decreases expressions of bone morphogenetic protein and activin membrane-bound inhibitor, Wnt10B, P53, and Bcl-2 and decreased proliferation, migration, and invasion capabilities, while increases in the apoptosis rate, expressions of vascular endothelial growth factor, Fas, Bax, Caspase-3, and cleaved Caspase-3; however, downregulated levels of TOPflash activity and β-catenin expression were recorded. The miR-708 inhibitors group displayed an opposite trend.Conclusion:Downregulation of miR-708-targeted bone morphogenetic protein and activin membrane-bound inhibitor inhibits the proliferation and migration of melanoma cells through the activation of the transforming growth factor β pathway and the suppression of Wnt pathway.

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Section: Introductionmentioning

confidence: 99%

RETRACTION: Mechanism of MicroRNA-708 Targeting BAMBI in Cell Proliferation, Migration, and Apoptosis in Mice With Melanoma via the Wnt and TGF-β Signaling Pathways

Yan

Jin

et al. 2018

Technol Cancer Res Treat

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“…To elucidate more extensively the genetic background of variable activity of ERK1/2 in melanoma cells, we analyzed the mutation status of other genes related to the MAPK signaling pathway (Figure A and Table S3). At least one potentially damaging mutation in genes encoding FGF receptors was found in six melanoma cell lines, including a G388R substitution in FGFR4 identified as one of germline determinants of clinical outcome of melanoma . In addition, the EGFR R521K variant (rs2227983) was found in all melanoma cell lines, besides DMBC33.…”

Section: Resultsmentioning

confidence: 99%

Whole‐exome sequencing reveals novel genetic variants associated with diverse phenotypes of melanoma cells

Hartman

Sztiller-Sikorska

Czyż

2019

Molecular Carcinogenesis

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We have extensively studied the phenotypic heterogeneity of patient-derived melanoma cells. Here, whole-exome sequencing revealed novel variants of genes associated with the MAPK, NOTCH, Hippo, cell-cycle, senescence, and ubiquitindependent pathways, which could contribute to the observed phenotypic diversity between cell lines. Focusing on mutations in the MAPK pathway-associated genes, we found BRAF (BRAF V600E ) and RAS subtypes, including NRAS Q61R and the rare HRAS Q61R variant, and additional alterations potentially leading to different ERK1/2 activity. Both RAS Q61R cell lines harbored a MEK1 P124S variant and exerted a low level of phospho-MEK1/2. Activity of the MAPK pathway was further attenuated in NRAS Q61R /MEK P124S cells by trametinib, and this effect was also shown in HRAS Q61R / MEK P124S melanoma cells. The observed variability in doubling time might be a consequence of diverse MAPK and PI3K/AKT pathway activities, but not exclusively, as a senescence program was also executed to different extent in distinct melanoma cell lines. Low percentages of senescent cells might result from mutations in CDKN2A, E2F3, and EZH2, and a high c-MYC expression. Vemurafenib and trametinib induced senescence concomitantly with c-MYC downregulation and irrespectively of CDKN2A mutation, but the EZH2 S412C variant might limit senescence induction. Damaging alterations in Hippo pathway-associated genes were accompanied with variability in the phosphorylation level of YAP1/TAZ and CTGF expression. Our study also suggests opposite activity of NOTCH2 F1209V and NOTCH2 N2002S variants. Additionally, we found a novel FBXW7 V418M variant that retained its function in melanoma cells. The obtained molecular data might be further exploited in genotype-phenotype relationship studies and in identifying novel biomarkers and therapies for melanomas.

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“…Despite the steady increase of prevalence, cutaneous melanoma is still defined as the most fatal form of skin cancer due to the incremental advances in early diagnostic modalities . In this study, we identified a crucial tumor‐suppressive miRNA, miR‐23a, which exerted an important role in melanoma.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐23a inhibits melanoma cell proliferation, migration, and invasion in mice through a negative feedback regulation of sdcbp and the MAPK/ERK signaling pathway

2018

IUBMB Life

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Melanoma is the main cause of death associated with skin cancer. Surgical resection and adjuvant therapy are currently effective treatments, but the recurrence rate is very high. The understanding of microRNA (miR) dynamics after surgical resection of melanoma is essential to accurately explain the changes in the recurrence of melanoma. In this study, we hypothesized that microRNA‐23a (miR‐23a) affects the cell proliferation, migration, and invasion of melanoma with a mechanism related to SDCBP and the MAPK/ERK signaling pathway. To validate this, we performed a series of experiments in cells of melanoma modeled. Initially, positive expression of SDCBP and morphology of normal and melanoma tissues and cells were observed. Expression of miR‐23a, SDCBP, and MAPK/ERK signaling pathway‐related genes was identified in melanoma tissues. Melanoma cells transfected with mimic or inhibitor of miR‐23a or si‐SDCBP were detected to validate effect of miR‐23a on SDCBP and the MAPK/ERK signaling pathway. MTT assay, scratch test, transwell assay, and flow cytometry were performed to evaluate cell viability, invasion, metastasis, and apoptosis in vitro, respectively. Tumorigenicity assay in nude mice was conducted to test the tumorigenesis of the transfected cells in vivo. High positive expression of SDCBP and abnormal morphology were observed in melanoma tissues and cells. Reduced expression of miR‐23a and increased expression of SDCBP and MAPK/ERK signaling pathway‐related genes were identified in the melanoma tissues of melanoma mice. Overexpressed miR‐23a dampened SDCBP and the MAPK/ERK signaling pathway. The melanoma cells with overexpressed miR‐23a presented ascended cell apoptosis and descended cell proliferation, migration, invasion as well as tumor size. Taken together, our study demonstrated that miR‐23a could inhibit the development of melanoma in mice through a negative feedback regulation of SDCBP and the MAPK/ERK signaling pathway. © 2018 IUBMB Life, 71(5):587–600, 2019

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Germline determinants of clinical outcome of cutaneous melanoma

Cited by 12 publications

References 90 publications

RETRACTION: Mechanism of MicroRNA-708 Targeting BAMBI in Cell Proliferation, Migration, and Apoptosis in Mice With Melanoma via the Wnt and TGF-β Signaling Pathways

RETRACTION: Mechanism of MicroRNA-708 Targeting BAMBI in Cell Proliferation, Migration, and Apoptosis in Mice With Melanoma via the Wnt and TGF-β Signaling Pathways

Whole‐exome sequencing reveals novel genetic variants associated with diverse phenotypes of melanoma cells

MicroRNA‐23a inhibits melanoma cell proliferation, migration, and invasion in mice through a negative feedback regulation of sdcbp and the MAPK/ERK signaling pathway

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