ncRNAs to Target Molecular Pathways

A special issue of Non-Coding RNA (ISSN 2311-553X).

Deadline for manuscript submissions: closed (27 June 2023) | Viewed by 14740

Special Issue Editors


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Guest Editor
Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Interests: small interfering RNA; experimental therapeutics; cancer; apoptosis

E-Mail Website
Guest Editor
Experimental Therapeutics Department, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Interests: non-coding RNA; chemoresistance; ovarian cancer; cancer therapy; RNA-binding proteins

Special Issue Information

Dear Colleagues,

The human genome is composed of approximately 3 billion nucleotides, but only about 2% of them are known to encode proteins. The other 98–99% of nucleotides are a black box known as non-coding RNAs (ncRNAs). These ncRNAs are diverse and may include microRNA (miRNA), small interfering RNAs (siRNAs), piwi-interacting RNAs (piRNAs), long ncRNAs, promoter-associated transcripts (PATs), enhancer RNAs (eRNAs), and circular RNAs (circRNAs). In this Special Edition, we will attempt to make sense of the many functions and potential functions of ncRNAs.

Prof. Dr. Gabriel Lopez-Berestein
Dr. Cristian Rodríguez-Aguayo
Guest Editors

Manuscript Submission Information

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Keywords

  • ncRNAs
  • cell signaling
  • microenvironmental signaling
  • aptamers

Published Papers (7 papers)

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Research

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16 pages, 4048 KiB  
Article
Inverse Impact of Cancer Drugs on Circular and Linear RNAs in Breast Cancer Cell Lines
by Anna Terrazzan, Francesca Crudele, Fabio Corrà, Pietro Ancona, Jeffrey Palatini, Nicoletta Bianchi and Stefano Volinia
Non-Coding RNA 2023, 9(3), 32; https://doi.org/10.3390/ncrna9030032 - 19 May 2023
Viewed by 1892
Abstract
Altered expression of circular RNAs (circRNAs) has previously been investigated in breast cancer. However, little is known about the effects of drugs on their regulation and relationship with the cognate linear transcript (linRNA). We analyzed the dysregulation of both 12 cancer-related circRNAs and [...] Read more.
Altered expression of circular RNAs (circRNAs) has previously been investigated in breast cancer. However, little is known about the effects of drugs on their regulation and relationship with the cognate linear transcript (linRNA). We analyzed the dysregulation of both 12 cancer-related circRNAs and their linRNAs in two breast cancer cell lines undergoing various treatments. We selected 14 well-known anticancer agents affecting different cellular pathways and examined their impact. Upon drug exposure circRNA/linRNA expression ratios increased, as a result of the downregulation of linRNA and upregulation of circRNA within the same gene. In this study, we highlighted the relevance of identifying the drug-regulated circ/linRNAs according to their oncogenic or anticancer role. Interestingly, VRK1 and MAN1A2 were increased by several drugs in both cell lines. However, they display opposite effects, circ/linVRK1 favors apoptosis whereas circ/linMAN1A2 stimulates cell migration, and only XL765 did not alter the ratio of other dangerous circ/linRNAs in MCF-7. In MDA-MB-231 cells, AMG511 and GSK1070916 decreased circGFRA1, as a good response to drugs. Furthermore, some circRNAs might be associated with specific mutated pathways, such as the PI3K/AKT in MCF-7 cells with circ/linHIPK3 correlating to cancer progression and drug-resistance, or NHEJ DNA repair pathway in TP-53 mutated MDA-MB-231 cells. Full article
(This article belongs to the Special Issue ncRNAs to Target Molecular Pathways)
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13 pages, 2539 KiB  
Article
Therapeutic Effects of WT1 Silencing via Respiratory Administration of Neutral DOPC Liposomal-siRNA in a Lung Metastasis Melanoma Murine Model
by Martin R. Ramos-Gonzalez, Eduardo Vazquez-Garza, Gerardo Garcia-Rivas, Cristian Rodriguez-Aguayo and Arturo Chavez-Reyes
Non-Coding RNA 2023, 9(2), 21; https://doi.org/10.3390/ncrna9020021 - 22 Mar 2023
Cited by 1 | Viewed by 1904
Abstract
The lungs represent a frequent target for metastatic melanoma as they offer a high-oxygen environment for tumor development. The overexpression of the WT1 protein has been associated with the occurrence of melanoma. In this study, we evaluated the effects of silencing the WT1 [...] Read more.
The lungs represent a frequent target for metastatic melanoma as they offer a high-oxygen environment for tumor development. The overexpression of the WT1 protein has been associated with the occurrence of melanoma. In this study, we evaluated the effects of silencing the WT1 protein by siRNA in both in vitro in the B16F10 melanoma cell line and in vivo in a murine model of lung metastatic melanoma. We did this by implementing a novel respiratory delivery strategy of a neutral DOPC liposomal-siRNA system (L-siRNA). In vitro studies showed an effective silencing of the WT1 protein in the siRNAs’ WT1-treated cells when compared with controls, resulting in a loss of the cell’s viability and proliferation by inducing G1 arrest, the inhibition of the migration and invasion capacities of the cells, as well as the induction of apoptosis. In vivo, the respiratory administration of L-WT1 siRNA showed an efficient biodistribution on the lungs. After two weeks of treatment, the silencing of the WT1 protein resulted in an important antitumor activity that reduced the tumor weight. In the survival study, L-WT1 treatment could significantly delay the death of the animals. This work demonstrates the efficacy of the L-siRNA respiratory administration as a novel therapy to reduce pulmonary tumors and to increase survivability by silencing specific cancer oncogenes as WT1. Full article
(This article belongs to the Special Issue ncRNAs to Target Molecular Pathways)
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Review

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23 pages, 1544 KiB  
Review
An Overview of the Immune Modulatory Properties of Long Non-Coding RNAs and Their Potential Use as Therapeutic Targets in Cancer
by Moises Martinez-Castillo, Abdelrahman M. Elsayed, Gabriel López-Berestein, Paola Amero and Cristian Rodríguez-Aguayo
Non-Coding RNA 2023, 9(6), 70; https://doi.org/10.3390/ncrna9060070 - 11 Nov 2023
Cited by 1 | Viewed by 1567
Abstract
Long non-coding RNAs (lncRNAs) play pivotal roles in regulating immune responses, immune cell differentiation, activation, and inflammatory processes. In cancer, they are gaining prominence as potential therapeutic targets due to their ability to regulate immune checkpoint molecules and immune-related factors, suggesting avenues for [...] Read more.
Long non-coding RNAs (lncRNAs) play pivotal roles in regulating immune responses, immune cell differentiation, activation, and inflammatory processes. In cancer, they are gaining prominence as potential therapeutic targets due to their ability to regulate immune checkpoint molecules and immune-related factors, suggesting avenues for bolstering anti-tumor immune responses. Here, we explore the mechanistic insights into lncRNA-mediated immune modulation, highlighting their impact on immunity. Additionally, we discuss their potential to enhance cancer immunotherapy, augmenting the effectiveness of immune checkpoint inhibitors and adoptive T cell therapies. LncRNAs as therapeutic targets hold the promise of revolutionizing cancer treatments, inspiring further research in this field with substantial clinical implications. Full article
(This article belongs to the Special Issue ncRNAs to Target Molecular Pathways)
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36 pages, 2401 KiB  
Review
Non-Coding RNAs: Foes or Friends for Targeting Tumor Microenvironment
by Anna Szymanowska, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein and Paola Amero
Non-Coding RNA 2023, 9(5), 52; https://doi.org/10.3390/ncrna9050052 - 28 Aug 2023
Cited by 2 | Viewed by 1797
Abstract
Non-coding RNAs (ncRNAs) are a group of molecules critical for cell development and growth regulation. They are key regulators of important cellular pathways in the tumor microenvironment. To analyze ncRNAs in the tumor microenvironment, the use of RNA sequencing technology has revolutionized the [...] Read more.
Non-coding RNAs (ncRNAs) are a group of molecules critical for cell development and growth regulation. They are key regulators of important cellular pathways in the tumor microenvironment. To analyze ncRNAs in the tumor microenvironment, the use of RNA sequencing technology has revolutionized the field. The advancement of this technique has broadened our understanding of the molecular biology of cancer, presenting abundant possibilities for the exploration of novel biomarkers for cancer treatment. In this review, we will summarize recent achievements in understanding the complex role of ncRNA in the tumor microenvironment, we will report the latest studies on the tumor microenvironment using RNA sequencing, and we will discuss the potential use of ncRNAs as therapeutics for the treatment of cancer. Full article
(This article belongs to the Special Issue ncRNAs to Target Molecular Pathways)
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31 pages, 1440 KiB  
Review
Targeting miRNAs and Other Non-Coding RNAs as a Therapeutic Approach: An Update
by Emine Bayraktar, Recep Bayraktar, Hulya Oztatlici, Gabriel Lopez-Berestein, Paola Amero and Cristian Rodriguez-Aguayo
Non-Coding RNA 2023, 9(2), 27; https://doi.org/10.3390/ncrna9020027 - 13 Apr 2023
Cited by 21 | Viewed by 2922
Abstract
Since the discovery of the first microRNAs (miRNAs, miRs), the understanding of miRNA biology has expanded substantially. miRNAs are involved and described as master regulators of the major hallmarks of cancer, including cell differentiation, proliferation, survival, the cell cycle, invasion, and metastasis. Experimental [...] Read more.
Since the discovery of the first microRNAs (miRNAs, miRs), the understanding of miRNA biology has expanded substantially. miRNAs are involved and described as master regulators of the major hallmarks of cancer, including cell differentiation, proliferation, survival, the cell cycle, invasion, and metastasis. Experimental data indicate that cancer phenotypes can be modified by targeting miRNA expression, and because miRNAs act as tumor suppressors or oncogenes (oncomiRs), they have emerged as attractive tools and, more importantly, as a new class of targets for drug development in cancer therapeutics. With the use of miRNA mimics or molecules targeting miRNAs (i.e., small-molecule inhibitors such as anti-miRS), these therapeutics have shown promise in preclinical settings. Some miRNA-targeted therapeutics have been extended to clinical development, such as the mimic of miRNA-34 for treating cancer. Here, we discuss insights into the role of miRNAs and other non-coding RNAs in tumorigenesis and resistance and summarize some recent successful systemic delivery approaches and recent developments in miRNAs as targets for anticancer drug development. Furthermore, we provide a comprehensive overview of mimics and inhibitors that are in clinical trials and finally a list of clinical trials based on miRNAs. Full article
(This article belongs to the Special Issue ncRNAs to Target Molecular Pathways)
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14 pages, 954 KiB  
Review
CircRNAs and RNA-Binding Proteins Involved in the Pathogenesis of Cancers or Central Nervous System Disorders
by Yuka Ikeda, Sae Morikawa, Moeka Nakashima, Sayuri Yoshikawa, Kurumi Taniguchi, Haruka Sawamura, Naoko Suga, Ai Tsuji and Satoru Matsuda
Non-Coding RNA 2023, 9(2), 23; https://doi.org/10.3390/ncrna9020023 - 31 Mar 2023
Cited by 10 | Viewed by 2642
Abstract
Circular RNAs (circRNAs), a newly recognized group of noncoding RNA transcripts, have established widespread attention due to their regulatory role in cell signaling. They are covalently closed noncoding RNAs that form a loop, and are typically generated during the splicing of precursor RNAs. [...] Read more.
Circular RNAs (circRNAs), a newly recognized group of noncoding RNA transcripts, have established widespread attention due to their regulatory role in cell signaling. They are covalently closed noncoding RNAs that form a loop, and are typically generated during the splicing of precursor RNAs. CircRNAs are key post-transcriptional and post-translational regulators of gene expression programs that might influence cellular response and/or function. In particular, circRNAs have been considered to function as sponges of specific miRNA, regulating cellular processes at the post-transcription stage. Accumulating evidence has shown that the aberrant expression of circRNAs could play a key role in the pathogenesis of several diseases. Notably, circRNAs, microRNAs, and several RNA-binding proteins, including the antiproliferative (APRO) family proteins, could be indispensable gene modulators, which might be strongly linked to the occurrence of diseases. In addition, circRNAs have attracted general interest for their stability, abundance in the brain, and their capability to cross the blood–brain barrier. Here, we present the current findings and theragnostic potentials of circRNAs in several diseases. With this, we aim to provide new insights to support the development of novel diagnostic and/or therapeutic strategies for these diseases. Full article
(This article belongs to the Special Issue ncRNAs to Target Molecular Pathways)
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Other

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15 pages, 1507 KiB  
Systematic Review
Conservation and Targets of miR-71: A Systematic Review and Meta-Analysis
by Devin Naidoo, Ryan Brennan and Alexandre de Lencastre
Non-Coding RNA 2023, 9(4), 41; https://doi.org/10.3390/ncrna9040041 - 26 Jul 2023
Viewed by 1334
Abstract
MicroRNAs (miRNAs) perform a pivotal role in the regulation of gene expression across the animal kingdom. As negative regulators of gene expression, miRNAs have been shown to function in the genetic pathways that control many biological processes and have been implicated in roles [...] Read more.
MicroRNAs (miRNAs) perform a pivotal role in the regulation of gene expression across the animal kingdom. As negative regulators of gene expression, miRNAs have been shown to function in the genetic pathways that control many biological processes and have been implicated in roles in human disease. First identified as an aging-associated gene in C. elegans, miR-71, a miRNA, has a demonstrated capability of regulating processes in numerous different invertebrates, including platyhelminths, mollusks, and insects. In these organisms, miR-71 has been shown to affect a diverse range of pathways, including aging, development, and immune response. However, the exact mechanisms by which miR-71 regulates these pathways are not completely understood. In this paper, we review the identified functions of miR-71 across multiple organisms, including identified gene targets, pathways, and the conditions which affect regulatory action. Additionally, the degree of conservation of miR-71 in the evaluated organisms and the conservation of their predicted binding sites in target 3′ UTRs was measured. These studies may provide an insight on the patterns, interactions, and conditions in which miR-71 is able to exert genotypic and phenotypic influence. Full article
(This article belongs to the Special Issue ncRNAs to Target Molecular Pathways)
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