Reciprocal Changes in miRNA Expression with Pigmentation and Decreased Proliferation Induced in Mouse B16F1 Melanoma Cells by l-Tyrosine and 5-Bromo-2′-Deoxyuridine

Autor: Esther Natalia Muñoz, Michael Carvajal, Daniel Osuna, Hernán Mauricio Rivera, Luis Alberto Gómez, Mauro Florez
Rok vydání: 2021
Předmět:
0301 basic medicine
senescence
Melanoma
Experimental

lcsh:Chemistry
Melanin
Mice
0302 clinical medicine
Gene Regulatory Networks
RNA-Seq
lcsh:QH301-705.5
Cellular Senescence
Spectroscopy
Pigmentation
Melanoma
l-tyrosine
General Medicine
Cell cycle
Microphthalmia-associated transcription factor
Phenotype
melanin
Computer Science Applications
Cell biology
Gene Expression Regulation
Neoplastic

5-bromo-2′-deoxyuridine
030220 oncology & carcinogenesis
miRNAs
Senescence
Biology
Article
Catalysis
Inorganic Chemistry
03 medical and health sciences
Cyclin D1
Cell Line
Tumor

microRNA
melanoma
medicine
Animals
Physical and Theoretical Chemistry
Molecular Biology
Cell Proliferation
Melanins
Organic Chemistry
medicine.disease
MicroRNAs
030104 developmental biology
Bromodeoxyuridine
lcsh:Biology (General)
lcsh:QD1-999
Tyrosine
Zdroj: International Journal of Molecular Sciences, Vol 22, Iss 1591, p 1591 (2021)
International Journal of Molecular Sciences
Volume 22
Issue 4
ISSN: 1422-0067
Popis: Background: Many microRNAs have been identified as critical mediators in the progression of melanoma through its regulation of genes involved in different cellular processes such as melanogenesis, cell cycle control, and senescence. However, microRNAs’ concurrent participation in syngeneic mouse B16F1 melanoma cells simultaneously induced decreased proliferation and differential pigmentation by exposure to 5-Brd-2′-dU (5’Bromo-2-deoxyuridine) and L-Tyr (L-Tyrosine) respectively, is poorly understood. Aim: To evaluate changes in the expression of microRNAs and identify which miRNAs in-network may contribute to the functional bases of phenotypes of differential pigmentation and reduction of proliferation in B16F1 melanoma cells exposed to 5-Brd-2′-dU and L-Tyr. Methods: Small RNAseq evaluation of the expression profiles of miRNAs in B16F1 melanoma cells exposed to 5-Brd-2′-dU (2.5 μg/mL) and L-Tyr (5 mM), as well as the expression by qRT-PCR of some molecular targets related to melanogenesis, cell cycle, and senescence. By bioinformatic analysis, we constructed network models of regulation and co-expression of microRNAs. Results: We confirmed that stimulation or repression of melanogenesis with L-Tyr or 5-Brd-2′-dU, respectively, generated changes in melanin concentration, reduction in proliferation, and changes in expression of microRNAs 470-3p, 470-5p, 30d-5p, 129-5p, 148b-3p, 27b-3p, and 211-5p, which presented patterns of coordinated and reciprocal co-expression, related to changes in melanogenesis through their putative targets Mitf, Tyr and Tyrp1, and control of cell cycle and senescence: Cyclin D1, Cdk2, Cdk4, p21, and p27. Conclusions: These findings provide insights into the molecular biology of melanoma of the way miRNAs are coordinated and reciprocal expression that may operate in a network as molecular bases for understanding changes in pigmentation and decreased proliferation induced in B16F1 melanoma cells exposed to L-Tyr and 5-Brd-2′-dU.
Databáze: OpenAIRE