scholarly journals MiR-375 Regulation of LDHB Plays Distinct Roles in Polyomavirus-Positive and -Negative Merkel Cell Carcinoma

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 443 ◽  
Author(s):  
Satendra Kumar ◽  
Hong Xie ◽  
Patrick Scicluna ◽  
Linkiat Lee ◽  
Viveca Björnhagen ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Merkel Cell Carcinoma ◽  
Normal Skin ◽  
Ectopic Expression ◽  
Growth Effect ◽  
Merkel Cell ◽  
Multiple Tumor ◽  
Induced Apoptosis

MicroRNA-375 (miR-375) is deregulated in multiple tumor types and regulates important targets involved in tumorigenesis and metastasis. This miRNA is highly expressed in Merkel cell carcinoma (MCC) compared to normal skin and other non-MCC skin cancers, and its expression is high in Merkel cell polyomavirus (MCPyV)-positive (MCPyV+) and low in MCPyV-negative (MCPyV−) MCC tumors. In this study, we characterized the function and target of miR-375 in MCPyV+ and MCPyV− MCC cell lines. Ectopic expression of miR-375 in MCPyV− MCC cells resulted in decreased cell proliferation and migration, as well as increased cell apoptosis and cell cycle arrest. However, in MCPyV+ MCC cells, inhibition of miR-375 expression reduced cell growth and induced apoptosis. Additionally, the expression of lactate dehydrogenase B (LDHB), a known target of miR-375, was inversely correlated with miR-375. Silencing of LDHB reduced cell growth in MCPyV− cell lines, while its silencing in MCPyV+ cell lines rescued the cell growth effect mediated by miR-375 inhibition. Together, our results suggest dual roles of miR-375 and LDHB in MCPyV and non-MCPyV-associated MCCs. We propose that LDHB could be a therapeutic target in MCC and different strategies should be applied in virus- and non-virus-associated MCCs.

scholarly journals Combining DNA Damage Induction with BCL-2 Inhibition to Enhance Merkel Cell Carcinoma Cytotoxicity

Biology ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 35 ◽  
Author(s):  
Wei Liu ◽  
Nathan A. Krump ◽  
Meenhard Herlyn ◽  
Jianxin You
Keyword(s):  
Dna Damage ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Merkel Cell Carcinoma ◽  
Human Fibroblasts ◽  
Immune Checkpoint Blockade ◽  
Merkel Cell ◽  
Basal Expression ◽  
Induced Apoptosis ◽  
Parp 1

Merkel cell carcinoma (MCC) is a highly lethal skin cancer. MCC tumors rapidly develop resistance to the chemotherapies tested to date. While PD-1/PD-L1 immune checkpoint blockade has demonstrated success in MCC treatment, a significant portion of MCC patients are nonresponsive. Therefore, the pressing need for effective MCC chemotherapies remains. We screened a library of natural products and discovered that one compound, glaucarubin, potently reduced the viability of Merkel cell polyomavirus (MCPyV)-positive MCCs, while remaining nontoxic to primary human fibroblasts and MCPyV-negative MCC cell lines tested. Protein array and Western blot analyses revealed that glaucarubin induces DNA damage and PARP-1 cleavage that correlates with the loss of viability in MCC cells. However, high basal expression of the antiapoptotic factor BCL-2 allowed a subpopulation of cells to survive glaucarubin treatment. Previous studies have shown that, while targeting BCL-2 family proteins significantly decreases MCC cell viability, BCL-2 antisense therapy alone was insufficient to inhibit tumor growth in patients with advanced MCC. We discovered that treatment with an FDA-approved BCL-2 inhibitor in the context of glaucarubin-induced DNA damage led to near complete killing in multiple MCPyV-positive MCC cell lines that express high levels of BCL-2. The combination of DNA damage-induced apoptosis and BCL-2 inhibition thus represents a novel therapeutic strategy for MCPyV-positive MCCs.

scholarly journals 098 Co-expression of epidermal keratins and neuroendocrine markers in Merkel cell carcinoma tumors and cell lines

2016 ◽  
Vol 136 (5) ◽  
pp. S18
Author(s):  
D. Mangelberger ◽  
M.E. Verhaegen ◽  
P.W. Harms ◽  
A. Durham ◽  
J.H. Kozlow ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Cell Lines ◽  
Merkel Cell Carcinoma ◽  
Merkel Cell ◽  
Neuroendocrine Markers

scholarly journals Characterization of the Merkel Cell Carcinoma miRNome

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Matthew S. Ning ◽  
Annette S. Kim ◽  
Nripesh Prasad ◽  
Shawn E. Levy ◽  
Huiqiu Zhang ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Normal Skin ◽  
Merkel Cell ◽  
Tissue Samples ◽  
Qrt Pcr ◽  
Skin Cancers ◽  
Next Generation Sequencing Ngs

MicroRNAs have been implicated in various skin cancers, including melanoma, squamous cell carcinoma, and basal cell carcinoma; however, the expression of microRNAs and their role in Merkel cell carcinoma (MCC) have yet to be explored in depth. To identify microRNAs specific to MCC (MCC-miRs), next-generation sequencing (NGS) of small RNA libraries was performed on different tissue samples including MCCs, other cutaneous tumors, and normal skin. Comparison of the profiles identified several microRNAs upregulated and downregulated in MCC. For validation, their expression was measured via qRT-PCR in a larger group of MCC and in a comparison group of non-MCC cutaneous tumors and normal skin. Eight microRNAs were upregulated in MCC: miR-502-3p, miR-9, miR-7, miR-340, miR-182, miR-190b, miR-873, and miR-183. Three microRNAs were downregulated: miR-3170, miR-125b, and miR-374c. Many of these MCC-miRs, the miR-183/182/96a cistron in particular, have connections to tumorigenic pathways implicated in MCC pathogenesis.In situhybridization confirmed that the highly expressed MCC-miR, miR-182, is localized within tumor cells. Furthermore, NGS and qRT-PCR reveal that several of these MCC-miRs are highly expressed in the patient-derived MCC cell line, MS-1. These data indicate that we have identified a set of MCC-miRs with important implications for MCC research.

Characterisation of four merkel cell carcinoma adherent cell lines

1995 ◽  
Vol 60 (1) ◽  
pp. 100-107 ◽  
Author(s):  
J. Helen Leonard ◽  
Peter Dash ◽  
Peter Holland ◽  
John H. Kearsley ◽  
John R. Bell
Keyword(s):  
Cell Carcinoma ◽  
Cell Lines ◽  
Merkel Cell Carcinoma ◽  
Adherent Cell ◽  
Merkel Cell

Secretomic analysis of extracellular vesicles originating from polyomavirus-negative and polyomavirus-positive Merkel cell carcinoma cell lines

PROTEOMICS ◽  
2016 ◽  
Vol 16 (19) ◽  
pp. 2587-2591 ◽  
Author(s):  
Aelita Konstantinell ◽  
Jack-Ansgar Bruun ◽  
Randi Olsen ◽  
Augusta Aspar ◽  
Nataša Škalko-Basnet ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Cell Lines ◽  
Extracellular Vesicles ◽  
Merkel Cell Carcinoma ◽  
Carcinoma Cell ◽  
Merkel Cell ◽  
Carcinoma Cell Lines

The novel AKT inhibitor Afuresertib suppresses human Merkel cell carcinoma MKL‐1 cell growth

2021 ◽  
Author(s):  
J.H. Wu ◽  
A.L. Limmer ◽  
D. Narayanan ◽  
H.Q. Doan ◽  
R.A. Simonette ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
The Novel ◽  
Merkel Cell ◽  
Akt Inhibitor

scholarly journals DNA-methylation patterns imply a common cellular origin of virus- and UV-associated Merkel cell carcinoma

Oncogene ◽  
2021 ◽  
Author(s):  
Jan Gravemeyer ◽  
Ivelina Spassova ◽  
Monique E. Verhaegen ◽  
Andrzej A. Dlugosz ◽  
Daniel Hoffmann ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Merkel Cell Carcinoma ◽  
Marker Genes ◽  
Methylation Data ◽  
Merkel Cell ◽  
Scoring Model ◽  
Methylation Patterns ◽  
Neuroendocrine Cancers

AbstractMerkel cell carcinoma (MCC) is a neuroendocrine tumor either induced by integration of the Merkel cell polyomavirus into the cell genome or by accumulation of UV-light-associated mutations (VP-MCC and UV-MCC). Whether VP- and UV-MCC have the same or different cellular origins is unclear; with mesenchymal or epidermal origins discussed. DNA-methylation patterns have a proven utility in determining cellular origins of cancers. Therefore, we used this approach to uncover evidence regarding the cell of origin of classical VP- and UV-MCC cell lines, i.e., cell lines with a neuroendocrine growth pattern (n = 9 and n = 4, respectively). Surprisingly, we observed high global similarities in the DNA-methylation of UV- and VP-MCC cell lines. CpGs of lower methylation in VP-MCC cell lines were associated with neuroendocrine marker genes such as SOX2 and INSM1, or linked to binding sites of EZH2 and SUZ12 of the polycomb repressive complex 2, i.e., genes with an impact on carcinogenesis and differentiation of neuroendocrine cancers. Thus, the observed differences appear to be rooted in viral compared to mutation-driven carcinogenesis rather than distinct cells of origin. To test this hypothesis, we used principal component analysis, to compare DNA-methylation data from different epithelial and non-epithelial neuroendocrine cancers and established a scoring model for epithelial and neuroendocrine characteristics. Subsequently, we applied this scoring model to the DNA-methylation data of the VP- and UV-MCC cell lines, revealing that both clearly scored as epithelial cancers. In summary, our comprehensive analysis of DNA-methylation suggests a common epithelial origin of UV- and VP-MCC cell lines.

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