Characterizing CD44 regulatory microRNAs as putative therapeutic agents in human melanoma

Fänder, Johannes; Kielstein, Heike; Büttner, Maximilian; Koelblinger, Peter; Dummer, Reinhard; Bauer, Marcus; Handke, Diana; Wickenhauser, Claudia; Seliger, Barbara; Jasinski‐Bergner, Simon

doi:10.18632/oncotarget.27305

Cited by 5 publications

(5 citation statements)

References 44 publications

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“…Based on the strong positive correlation between the factors involved in 2′-O-methylation and pseudouridylation with most of the clinical relevant proliferation markers, a possible correlation between these factors and prognostic marker genes relevant for MM was evaluated such as melanoma antigen recognized by T cells (MART)1, S100 calcium binding protein B (S100B), S100A4, S100A9, melanocyte inducing transcription factor (MITF), matrix metallopeptidase 2 (MMP2), nucleoside diphosphate kinase 1 (NM23), cluster of differentiation (CD) 44, premelanosome protein (PMEL), and BCL2 apoptosis regulator (BCL2) using the same TCGA data sets [ 39 , 40 , 41 , 42 , 43 ] ( Table 3 ). Next to these marker genes the invasion depth termed Breslow’s depth is of prognostic value.…”

Section: Resultsmentioning

confidence: 99%

“…The processes of 2′-O-methylation and pseudouridylation also occur in other RNA species with a strong impact to diverse molecular processes of malignant transformation and thus are of clinical relevance. These other RNA species include microRNAs (miRs), which are non-coding single stranded RNAs with an approximately length of ~22 nt [ 46 ], binding specifically and preferentially, but not exclusively, within the 3′- untranslated region (UTR) to their target mRNAs sequence [ 40 , 47 ] thereby causing a translational repression and mRNA decay [ 48 ].…”

Section: Resultsmentioning

confidence: 99%

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Relevance of 2′-O-Methylation and Pseudouridylation for the Malignant Melanoma

Jasinski‐Bergner

Blümke

Wickenhauser

et al. 2021

Cancers

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The two RNA modifications 2′-O-methylation and pseudouridylation occur on several RNA species including ribosomal RNAs leading to an increased translation as well as cell proliferation associated with distinct functions. Using malignant melanoma (MM) as a model system the proteins mediating these RNA modifications were for the first time analyzed by different bioinformatics tools and public available databases regarding their expression and histological localization. Next to this, the impact of these RNA-modifying factors on prognostic relevant processes and marker genes of malignant melanoma was investigated and correlated to immune surveillance and evasion strategies. The RNA modifying factors exerted statistically significant positive correlations to the expression of genes involved in cell proliferation and were statistically significant negative correlated to the expression of human leukocyte antigen class I genes as well as of components of the antigen processing machinery in malignant melanoma. Upregulation of the RNA modifying proteins was of prognostic relevance in this tumor disease with a negative impact on the overall survival of melanoma patients. Furthermore, the expression of known oncogenic miRs, which are induced in malignant melanoma, directly correlated to the expression of factors involved in these two RNA modifications.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Relevance of 2′-O-Methylation and Pseudouridylation for the Malignant Melanoma

Jasinski‐Bergner

Blümke

Wickenhauser

et al. 2021

Cancers

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“…However, several novel strategies using nanoparticles and targeting miRNAs are being developed [38][39][40][41].…”

Section: Discussionmentioning

confidence: 99%

Automated Quantification of CD44, c-MET, EGFR, MTOR, and GLUT1 Expression in Head and Neck Squamous Cell Carcinoma: The Impact of p16 Status and Response to Chemoradiation

Arden¹,

Quinn²,

Wilson³

et al. 2020

COR

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This study assessed automated quantification of CD44, c-MET, MTOR, EGFR, and GLUT1 protein expression in a tissue microarray of 109 Stage II-IV p16 positive and negative head and neck squamous cell carcinomas (HNSCC) treated with definitive chemoradiation. Immunohistochemistry-based protein expression was quantified in an automated manner using digitally scanned images processed with Definiens Tissue Studio software to generate a histologic score (H-score, range 0-300) which was normalized for each biomarker. Biomarker expression levels were correlated with one another and with p16 status. Effects of biomarker and p16 status on locoregional control, disease-free survival, and overall survival were analyzed using Kaplan Meier and Cox proportional hazard modelling. There was a significant negative correlation between CD44 and p16 expression and significant positive correlations between CD44 and MTOR, CD44 and GLUT1, c-MET and MTOR, and MTOR and GLUT1. When patients were stratified by p16 status, the significant positive correlation between CD44 expression and MTOR remained for both the p16 positive and negative subsets, while correlations between CD44 and GLUT1 and c-MET and MTOR were seen in the p16 negative subset only. A significant correlation between MTOR and GLUT was seen overall and for the p16 positive subset. When the effects of biomarker expression on clinical endpoints were examined, histologic scores below the defined cut-points for CD44 and c-MET were each associated with improved locoregional control. Higher expressions of CD44, c-MET, EGFR, and GLUT1 were associated with inferior disease-free and overall survival. On multivariable analysis, p16 positivity remained independently associated with improved locoregional control, disease-free survival, and overall survival, high CD44 remained independently associated with inferior locoregional control, disease-free survival, and overall survival, and EGFR with inferior disease-free and overall survival. In conclusion, the use of an automated system to quantify IHC expression allowed objective correlation between biomarkers and stratification of patients, revealing that higher expressions of CD44, c-MET, EGFR, and GLUT1 were associated with poorer disease-free and overall survival.

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“…This mixture was deemed more suitable for the study than the film-forming mixture that contained other excipients [10]. Cell lines were chosen because they highly expressed the CD44 transmembrane receptor [19][20][21]. CD44 is a cell surface glycoprotein overexpressed in many solid tumors including pancreatic, breast, ovarian, brain, and lung cancers.…”

Section: In Vitro Cytotoxicity Of the Cispt/naha Complexmentioning

confidence: 99%

In Vitro Assessment of Cisplatin/Hyaluronan Complex for Loco-Regional Chemotherapy

Banella,

Saraswat,

Patel

et al. 2023

IJMS

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Loco-regional chemotherapy is a strategy used to achieve more precise anticancer drug effect directly on tumor mass, while decreasing whole body exposure, which can lead to undesirable side effects. Thus, the loco-regional chemotherapy is conceptually similar to the targeted drug delivery systems for delivering chemotherapeutics to cancer cells in a certain location of the body. Recently, it has been demonstrated that a novel polymeric film containing the complex between cisplatin (cisPt) and hyaluronan (sodium salt of hyaluronic acid; NaHA) enhanced in vivo efficacy and safety of cisplatin (cisPt) by loco-regional delivery in pleural mesothelioma. Biologically, hyaluronic acid (HA) binds with the CD44 receptor, which is a transmembrane glycoprotein overexpressed by other cancer cells. Thus, administering both cisPt and hyaluronan together as a complex loco-regionally to the tumor site could target cancer cells locally and enhance treatment safety. A slight excess of hyaluronan was required to have more than 85% cisPt complexation. In cell monolayers (2D model) the cisPt/NaHA complex in solution demonstrated dose- and time-dependent cytotoxic effect by decreasing the viability of pancreatic, melanoma, and lung cell lines (they all express CD44). At the same concentration in solution, the complex was as effective as cisPt alone. However, when applied as film to melanoma spheroids (3D model), the complex was superior because it prevented the tumor spheroid growth and, more importantly, the formation of new cell colonies. Hence, cisPt/NaHA complex could work in preventing metastases loco-regionally and potentially avoiding systemic relapses.

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Characterizing CD44 regulatory microRNAs as putative therapeutic agents in human melanoma

Cited by 5 publications

References 44 publications

Relevance of 2′-O-Methylation and Pseudouridylation for the Malignant Melanoma

Relevance of 2′-O-Methylation and Pseudouridylation for the Malignant Melanoma

Automated Quantification of CD44, c-MET, EGFR, MTOR, and GLUT1 Expression in Head and Neck Squamous Cell Carcinoma: The Impact of p16 Status and Response to Chemoradiation

In Vitro Assessment of Cisplatin/Hyaluronan Complex for Loco-Regional Chemotherapy

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