Learning from Embryogenesis-A Comparative Expression Analysis in Melanoblast Differentiation and Tumorigenesis Reveals miRNAs Driving Melanoma Development

Linck-Paulus, Lisa and Laemmerhirt, Lisa and Voeller, Daniel and Meyer, Katharina and Engelmann, Julia C. and Spang, Rainer and Eichner, Norbert and Meister, Gunter and Kuphal, Silke and Bosserhoff, Anja Katrin (2021) Learning from Embryogenesis-A Comparative Expression Analysis in Melanoblast Differentiation and Tumorigenesis Reveals miRNAs Driving Melanoma Development. JOURNAL OF CLINICAL MEDICINE, 10 (11): 2259. ISSN , 2077-0383

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Abstract

Malignant melanoma is one of the most dangerous tumor types due to its high metastasis rates and a steadily increasing incidence. During tumorigenesis, the molecular processes of embryonic development, exemplified by epithelial-mesenchymal transition (EMT), are often reactivated. For melanoma development, the exact molecular differences between melanoblasts, melanocytes, and melanoma cells are not completely understood. In this study, we aimed to identify microRNAs (miRNAs) that promote melanoma tumorigenesis and progression, based on an in vitro model of normal human epidermal melanocyte (NHEM) de-differentiation into melanoblast-like cells (MBrCs). Using miRNA-sequencing and differential expression analysis, we demonstrated in this study that a majority of miRNAs have an almost equal expression level in NHEMs and MBrCs but are significantly differentially regulated in primary tumor- and metastasis-derived melanoma cell lines. Further, a target gene analysis of strongly regulated but functionally unknown miRNAs yielded the implication of those miRNAs in many important cellular pathways driving malignancy. We hypothesize that many of the miRNAs discovered in our study are key drivers of melanoma development as they account for the tumorigenic potential that differentiates melanoma cells from proliferating or migrating embryonic cells.

Item Type: Article
Uncontrolled Keywords: LEUKEMIA INHIBITORY FACTOR; CELL-LINES; CANCER; GROWTH; METASTASIS; TUMOR; PROGRESSION; MICRORNA-1246; MELANOCYTES; MIR-105; miRNAs; melanoma; embryogenesis; melanoblasts
Subjects: 500 Science > 570 Life sciences
600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang)
Informatics and Data Science > Lehrstuhl für Statistische Bioinformatik (Prof. Spang)

Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Gunter Meister
Depositing User: Dr. Gernot Deinzer
Date Deposited: 07 Sep 2022 11:41
Last Modified: 07 Sep 2022 11:41
URI: https://pred.uni-regensburg.de/id/eprint/46810

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