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Small Activating RNAs: Towards the Development of New Therapeutic Agents and Clinical Treatments

Ghanbarian, Hossein, Aghamiri, Shahin, Eftekhary, Mohamad, Wagner, Nicole, Wagner, Kay-Dietrich·2021·Cells
DOI 10.3390/cells10030591PMC PMC8001863
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Abstract

Small double-strand RNA (dsRNA) molecules can activate endogenous genes via an RNA-based promoter targeting mechanism. RNA activation (RNAa) is an evolutionarily conserved mechanism present in diverse eukaryotic organisms ranging from nematodes to humans. Small activating RNAs (saRNAs) involved in RNAa have been successfully used to activate gene expression in cultured cells, and thereby this emergent technique might allow us to develop various biotechnological applications, without the need to synthesize hazardous construct systems harboring exogenous DNA sequences. Accordingly, this thematic issue aims to provide insights into how RNAa cellular machinery can be harnessed to activate gene expression leading to a more effective clinical treatment of various diseases.

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Figure 1 Schematic illustration of the anticancer mechanism of saRNA (small activating RNA)-based therapeutics. At first, saRNAs are loaded on the AGO2 protein. Then AGO2 separates the passenger strand. After that, the complex of saRNA guide strand and AGO2 cross the nuclear and interact with promoter sequences of interested genes to increase transcription by methylation of H3K4 and/or demethylation of H3K9. The expression level of tumor suppressor genes is restored, resulting in induction of apoptosis, chemoresistance reversal, inhibition of invasion and metastasis, cell cycle arrest, and cellular senescence.
Figure 1 Schematic illustration of the anticancer mechanism of saRNA (small activating RNA)-based therapeutics. At first, saRNAs are loaded on the AGO2 protein. Then AGO2 separates the passenger strand. After that, the complex of saRNA guide strand and AGO2 cross the nuclear and interact with promoter sequences of interested genes to increase transcription by methylation of H3K4 and/or demethylation of H3K9. The expression level of tumor suppressor genes is restored, resulting in induction of apoptosis, chemoresistance reversal, inhibition of invasion and metastasis, cell cycle arrest, and cellular senescence.CC BY · PubMed Central

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Cited by

Metadata

Authors
Ghanbarian, H., Aghamiri, S., Eftekhary, M., Wagner, N., & Wagner, K.-D.
Venue
Cells
Publisher
MDPI AG
Published
2021-03-08
Volume
10
Issue
3
Pages
591
ISSN
2073-4409
DOI
10.3390/cells10030591
PMC
PMC8001863
Cited by
47
References
6
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)

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