microRNAs as Therapeutic Agents: From Basic Molecular Knowledge to Clinical Research

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "RNA".

Deadline for manuscript submissions: closed (15 December 2021) | Viewed by 6684

Special Issue Editors


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Guest Editor
1. H&TRC Health & Technology Research Center, ESTeSL—Escola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa, 1649-028, Lisboa, Portugal
2. Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal
Interests: microRNA; T cells; T cell differentiation; gene expression regulation

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Guest Editor
Faculdade de Medicina, Instituto de Medicina Molecular, Universidade de Lisboa, Lisboa, Portugal
Interests: non-coding RNAs; cardiovascular diseases; infectious diseases; cell-to-cell communication; circulating RNAs; biomarkers
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Special Issue Information

Dear Colleagues,

This issue aims at exploring the functional basis of microRNAs (miRNAs) as therapeutic agents either through basic research studies or in an applied context by exploring physiological phenotypes and dissecting the methods used for in vitro and in vivo manipulation of a potential therapeutic miRNA.

By targeting most of the mRNAs coded in the genome and by forming complex networks between them and their targets, microRNAs influence virtually every cellular, developmental, and homeostatic process in animals, as illustrated by the diverse phenotypes and pathologies caused by their absence or deregulation.

In fact, several miRNAs act either to limit or boost given biological responses, depending on whether overall, they repress positive or negative regulators. In a pathophysiological context, these responses might be relevant to fight a given condition.

Thus, either by mimicking or blocking miRNA function, it is possible to modulate the levels of these short RNA sequences with a potential use as therapeutical molecules. Special attention has been given to their use for the treatment of diseases such as immune-related diseases, infections, diabetes or cancer, where therapeutic agents based on miRNA manipulation have reached clinical stages.

In this issue of Genes, we aim at exploring basic mechanisms of miRNA- mediated modulation of gene expression and how this knowledge translates into clinical research namely, by exploring their use as therapeutic agents in diseases such as immune-related, diabetes or cancer, among others.

Prof. Dr. Anita Q. Gomes
Prof. Dr. Francisco J. Enguita
Guest Editors

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Keywords

  • miRNA biology and function
  • gene expression regulation
  • miRNA manipulation
  • miRNA-mediated therapy
  • miRNA in disease

Published Papers (2 papers)

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Research

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11 pages, 4329 KiB  
Article
The Role of the MYC/miR-150/MYB/ZDHHC11 Network in Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma
by Lotteke J. Y. M. Ziel-Swier, Yichen Liu, Annika Seitz, Debora de Jong, Jasper Koerts, Bea Rutgers, Rianne Veenstra, Fazlyn R. Abdul Razak, Agnieszka Dzikiewicz-Krawczyk, Anke van den Berg and Joost Kluiver
Genes 2022, 13(2), 227; https://doi.org/10.3390/genes13020227 - 25 Jan 2022
Cited by 3 | Viewed by 2543
Abstract
We previously described involvement of the MYC/miR-150/MYB/ZDHHC11 network in the growth of Burkitt lymphoma (BL) cells. Here we studied the relevance of this network in the two other B-cell lymphomas: Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL). Expression levels of the [...] Read more.
We previously described involvement of the MYC/miR-150/MYB/ZDHHC11 network in the growth of Burkitt lymphoma (BL) cells. Here we studied the relevance of this network in the two other B-cell lymphomas: Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL). Expression levels of the network components were assessed at the RNA and protein level. The effect of modulating levels of the network components on cell growth was determined through GFP competition assay. AGO2-RNA immunoprecipitation was performed to validate targeting by miR-150. Expression levels of MYC, MYB and ZDHHC11 were increased, while miR-150 levels were decreased similar to the pattern observed in BL. The knockdown of MYC, MYB and ZDHHC11 decreased the growth of HL and DLBCL cells. In contrast, overexpression of miR-150 did not induce clear phenotypes in HL, and limited the effects in DLBCL. This could not be explained by the differences in overexpression levels. Furthermore, we showed that in HL, ZDHHC11 and MYB are efficiently targeted by miR-150. To conclude, MYC, MYB and ZDHHC11 are critical for the growth of HL and DLBCL cells consistent with the role observed in BL cells, while low endogenous miR-150 levels appeared to be less critical for the growth of HL and DLBCL cells despite the effective targeting of ZDHHC11 and MYB. Full article
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Review

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22 pages, 1213 KiB  
Review
Therapeutic Metabolic Reprograming Using microRNAs: From Cancer to HIV Infection
by Mark S. Gibson, Cláudia Noronha-Estima and Margarida Gama-Carvalho
Genes 2022, 13(2), 273; https://doi.org/10.3390/genes13020273 - 29 Jan 2022
Cited by 4 | Viewed by 3383
Abstract
MicroRNAs (miRNAs) are crucial regulators of cellular processes, including metabolism. Attempts to use miRNAs as therapeutic agents are being explored in several areas, including the control of cancer progression. Recent evidence suggests fine tuning miRNA activity to reprogram tumor cell metabolism has enormous [...] Read more.
MicroRNAs (miRNAs) are crucial regulators of cellular processes, including metabolism. Attempts to use miRNAs as therapeutic agents are being explored in several areas, including the control of cancer progression. Recent evidence suggests fine tuning miRNA activity to reprogram tumor cell metabolism has enormous potential as an alternative treatment option. Indeed, cancer growth is known to be linked to profound metabolic changes. Likewise, the emerging field of immunometabolism is leading to a refined understanding of how immune cell proliferation and function is governed by glucose homeostasis. Different immune cell types are now known to have unique metabolic signatures that switch in response to a changing environment. T-cell subsets exhibit distinct metabolic profiles which underlie their alternative differentiation and phenotypic functions. Recent evidence shows that the susceptibility of CD4+ T-cells to HIV infection is intimately linked to their metabolic activity, with many of the metabolic features of HIV-1-infected cells resembling those found in tumor cells. In this review, we discuss the use of miRNA modulation to achieve metabolic reprogramming for cancer therapy and explore the idea that the same approach may serve as an effective mechanism to restrict HIV replication and eliminate infected cells. Full article
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