Low Drosha protein expression in cutaneous T‐cell lymphoma is associated with worse disease outcome

Gambichler, Thilo; Salveridou, K; Schmitz, Lutz; Käfferlein, Heiko U.; Brüning, Thomas; Stockfleth, Eggert; Sand, Michael; Lang, Kerstin

doi:10.1111/jdv.15652

Cited by 9 publications

(3 citation statements)

References 21 publications

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“…Reports in mycosis fungoides show that DPP4 expression predominates in the early stages of disease 123 and is lost with disease progression 123‐128 . Similarly, marked percentages of CD4 + CD26 − T lymphocytes are seen in advanced Sézary syndrome showing that both mycosis fungoides and Sézary syndrome have a consistent pattern of CD26 loss throughout disease course 123 .…”

Section: Cutaneous T‐cell Lymphomamentioning

confidence: 99%

The role of Dipeptidyl Peptidase‐4 in cutaneous disease

Patel

Jones

Kridin

et al. 2020

Experimental Dermatology

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Dipeptidyl peptidase-4 (DPP4) is a multifunctional, type II transmembrane glycoprotein expressed on the cell surface of many tissues. 1,2 Its soluble form (aa 49-766) is also found in various bodily fluids (Figure 1). 3 CD26 is a cell surface marker with DPP4 enzymatic activity in its extracellular domain. For uniformity, we will use the term CD26 + or CD26 − to indicate the presence or absence of DPP4 as a cell surface marker but use DPP4 in reference to the enzyme and gene/protein expression. Dipeptidyl peptidase-4 is a serine exopeptidase, which cleaves X-proline or X-alanine dipeptide residues in the penultimate position from the NH 2-terminus of polypeptide substrates, including chemokines, neuropeptides and hormones. 4-6 The cysteine-rich domain of DPP4 interacts with the proteins of the extracellular matrix whilst the glycosylation-rich domain interacts with adenosine deaminase and caveolin-1 amongst others. 5,7,8 DPP4 inhibitors (DPP4i) are best known for their role in the treatment of diabetes mellitus due to their ability to deactivate incretins, such as glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1. 9 The rise of DPP4 inhibitors, however, is also accompanied by undesired cardiovascular and dermatologic manifestations. 10-12 More recently, the role of DPP4 and its inhibition in various dermatoses including bullous pemphigoid, psoriasis and mycosis fungoides have been described. In this review, we sought to summarize the role of DPP4 expression, regulation, and inhibition in cutaneous diseases.

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Section: Cutaneous T‐cell Lymphomamentioning

confidence: 99%

The role of Dipeptidyl Peptidase‐4 in cutaneous disease

Patel

Jones

Kridin

et al. 2020

Experimental Dermatology

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“…Low Drosha expression seems to be an independent predictor biomarker for advanced stages. Moreover, this expression was associated with lymphoma-specific death, the authors pointing out the tumor suppressor gene function of Drosha (Gambichler et al, 2019).…”

Section: Cutaneous Lymphomamentioning

confidence: 97%

miRNAs in the Diagnosis and Prognosis of Skin Cancer

Neagu

Constantin

Creţoiu

et al. 2020

Front. Cell Dev. Biol.

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Skin cancer is, at present, the most common type of malignancy in the Caucasian population. Its incidence has increased rapidly in the last decade for both melanoma and non-melanoma skin cancer. Differential expression profiles of microRNAs (miRNAs) have been reported for a variety of different cancers, including skin cancers. Since miRNAs' discovery as regulators of gene expression, their importance grew in the field of oncology. miRNAs can post-transcriptionally regulate gene expression, tumor initiation, development progression, and aggressiveness. Nowadays, these short regulatory RNAs are perceived as one of the epigenetic markers for the identification of new diagnostic and/or prognostic molecular markers. Moreover, as miRNAs can drive tumorigenesis, they might eventually represent new therapy targets. Some miRNAs are pleiotropic, such as miR-214, which was found deregulated in several other tumors besides skin cancers. Some others are specific for one or more skin cancer types, like miR-21 and miR-221 for cutaneous melanoma and cutaneous squamous carcinoma or miR-155 for melanoma and cutaneous lymphoma. The goal of this review was to summarize some of the main miRNA detection technologies that are used to evaluate miRNAs in tissues and body fluids. Furthermore, their quantification limits, conformity, and robustness are discussed. Aberrant miRNA expression is analyzed for cutaneous melanoma, cutaneous squamous cell carcinoma (CSCC), skin lymphomas, cutaneous lymphoma, and Merkel cell carcinoma (MCC). In this type of disease, miRNAs are described as potential biomarkers to diagnose early lesion and/or early metastatic disease. In the future, whether in tissue or circulating in body fluids, miRNAs will gain their place in skin cancer diagnosis, prognosis, and future therapeutic targets.

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“…Moreover, dysregulation of the enzymes Dicer and Drosha, involved in miR biogenesis and processing, was reported in several cancers, resulting in defective processing and thus altered miR profiles in cancers [20]. Interestingly, increased expression of Dicer and reduced expression of Drosha was observed in CTCL, reflecting the complexity of miR dysregulation, which remains to be further understood [43,44].…”

Section: Dysregulation Of Mirs In Ctclmentioning

confidence: 99%

MicroRNAs in the Pathogenesis, Diagnosis, Prognosis and Targeted Treatment of Cutaneous T-Cell Lymphomas

Gluud

Willerslev-Olsen

Gjerdrum

et al. 2020

Cancers

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Cutaneous T-cell lymphoma (CTCL) represents a heterogeneous group of potentially devastating primary skin malignancies. Despite decades of intense research efforts, the pathogenesis is still not fully understood. In the early stages, both clinical and histopathological diagnosis is often difficult due to the ability of CTCL to masquerade as benign skin inflammatory dermatoses. Due to a lack of reliable biomarkers, it is also difficult to predict which patients will respond to therapy or progress towards severe recalcitrant disease. In this review, we discuss recent discoveries concerning dysregulated microRNA (miR) expression and putative pathological roles of oncogenic and tumor suppressive miRs in CTCL. We also focus on the interplay between miRs, histone deacetylase inhibitors, and oncogenic signaling pathways in malignant T cells as well as the impact of miRs in shaping the inflammatory tumor microenvironment. We highlight the potential use of miRs as diagnostic and prognostic markers, as well as their potential as therapeutic targets. Finally, we propose that the combined use of miR-modulating compounds with epigenetic drugs may provide a novel avenue for boosting the clinical efficacy of existing anti-cancer therapies in CTCL.

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Low Drosha protein expression in cutaneous T‐cell lymphoma is associated with worse disease outcome

Cited by 9 publications

References 21 publications

The role of Dipeptidyl Peptidase‐4 in cutaneous disease

The role of Dipeptidyl Peptidase‐4 in cutaneous disease

miRNAs in the Diagnosis and Prognosis of Skin Cancer

MicroRNAs in the Pathogenesis, Diagnosis, Prognosis and Targeted Treatment of Cutaneous T-Cell Lymphomas

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