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Article

miR-16-5p Promotes Erythroid Maturation of Erythroleukemia Cells by Regulating Ribosome Biogenesis

1
Laboratory of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece
2
FunPATH (Functional Proteomics and Systems Biology Research Group at AUTH) Research Group, KEDEK—Aristotle University of Thessaloniki, Balkan Center, GR-57001 Thessaloniki, Greece
3
Department of Life and Health Sciences, University of Nicosia, CY-1700 Nicosia, Cyprus
*
Author to whom correspondence should be addressed.
Academic Editors: Cristina Romero-López and Alfredo Berzal-Herranz
Pharmaceuticals 2021, 14(2), 137; https://doi.org/10.3390/ph14020137
Received: 9 January 2021 / Revised: 5 February 2021 / Accepted: 5 February 2021 / Published: 9 February 2021
(This article belongs to the Special Issue siRNA Therapeutics: From Bench Lab to Clinics)
miRNAs constitute a class of non-coding RNA that act as powerful epigenetic regulators in animal and plant cells. In order to identify putative tumor-suppressor miRNAs we profiled the expression of various miRNAs during differentiation of erythroleukemia cells. RNA was purified before and after differentiation induction and subjected to quantitative RT-PCR. The majority of the miRNAs tested were found upregulated in differentiated cells with miR-16-5p showing the most significant increase. Functional studies using gain- and loss-of-function constructs proposed that miR-16-5p has a role in promoting the erythroid differentiation program of murine erythroleukemia (MEL) cells. In order to identify the underlying mechanism of action, we utilized bioinformatic in-silico platforms that incorporate predictions for the genes targeted by miR-16-5p. Interestingly, ribosome constituents, as well as ribosome biogenesis factors, were overrepresented among the miR-16-5p predicted gene targets. Accordingly, biochemical experiments showed that, indeed, miR-16-5p could modulate the levels of independent ribosomal proteins, and the overall ribosomal levels in cultured cells. In conclusion, miR-16-5p is identified as a differentiation-promoting agent in erythroleukemia cells, demonstrating antiproliferative activity, likely as a result of its ability to target the ribosomal machinery and restore any imbalanced activity imposed by the malignancy and the blockade of differentiation. View Full-Text
Keywords: miRNA therapeutics; miR-16-5p; erythroleukemia; erythroid differentiation; cancer; ribosomes miRNA therapeutics; miR-16-5p; erythroleukemia; erythroid differentiation; cancer; ribosomes
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MDPI and ACS Style

Papagiannopoulos, C.I.; Theodoroula, N.F.; Vizirianakis, I.S. miR-16-5p Promotes Erythroid Maturation of Erythroleukemia Cells by Regulating Ribosome Biogenesis. Pharmaceuticals 2021, 14, 137. https://doi.org/10.3390/ph14020137

AMA Style

Papagiannopoulos CI, Theodoroula NF, Vizirianakis IS. miR-16-5p Promotes Erythroid Maturation of Erythroleukemia Cells by Regulating Ribosome Biogenesis. Pharmaceuticals. 2021; 14(2):137. https://doi.org/10.3390/ph14020137

Chicago/Turabian Style

Papagiannopoulos, Christos I., Nikoleta F. Theodoroula, and Ioannis S. Vizirianakis. 2021. "miR-16-5p Promotes Erythroid Maturation of Erythroleukemia Cells by Regulating Ribosome Biogenesis" Pharmaceuticals 14, no. 2: 137. https://doi.org/10.3390/ph14020137

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