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MiRNA-Mediated Mechanisms in the Generation of Effective and Safe Oncolytic Viruses.

ABSTRACT: MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression by inhibiting the translation of target transcripts. The expression profiles of miRNAs vary in different tissues and change with the development of diseases, including cancer. This feature has begun to be used for the modification of oncolytic viruses (OVs) in order to increase their selectivity and efficacy. OVs represent a relatively new class of anticancer drugs; they are designed to replicate in cancer tumors and destroy them. These can be natural viruses that can replicate within cancer tumor cells, or recombinant viruses created in laboratories. There are some concerns regarding OVs' toxicity, due to their ability to partially replicate in healthy tissues. In addition, lytic and immunological responses upon OV therapy are not always sufficient, so various OV editing methods are used. This review discusses the latest results of preclinical and clinical studies of OVs, modifications of which are associated with the miRNA-mediated mechanism of gene silencing.

SUBMITTER: Toropko M

PROVIDER: S-EPMC11360794 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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miRNA-Mediated Mechanisms in the Generation of Effective and Safe Oncolytic Viruses.

Toropko Mariia M Chuvpilo Sergey S Karabelsky Alexander A

Pharmaceutics 20240725 8

MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression by inhibiting the translation of target transcripts. The expression profiles of miRNAs vary in different tissues and change with the development of diseases, including cancer. This feature has begun to be used for the modification of oncolytic viruses (OVs) in order to increase their selectivity and efficacy. OVs represent a relatively new class of anticancer drugs; they are designed to replicate in cancer tumors and dest ...[more]

PMID: 39204331

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Project description:IntroductionOncolytic herpes simplex viruses (oHSVs) are a type of biotherapeutic utilized in cancer therapy due to their ability to selectively infect and destroy tumor cells without harming healthy cells. We sought to investigate the functional genomic response and altered metabolic pathways of human cancer cells to oHSV-1 infection and to elucidate the influence of these responses on the relationship between the virus and the cancer cells.MethodsTwo datasets containing gene expression profiles of tumor cells infected with oHSV-1 (G207) and non-infected cells from the Gene Expression Omnibus (GEO) database were processed and normalized using the R software. Common differentially expressed genes between datasets were selected to identify hub genes and were further analyzed. Subsequently, the expression of hub genes was verified by real-time polymerase chain reaction (qRT-PCR) in MDA-MB-231 (a breast cancer cell line) infected with oHSV-1 and non-infected cells.ResultsThe results of our data analysis indicated notable disparities in the genes associated with the proteasome pathway between infected and non-infected cells. Our ontology analysis revealed that the proteasome-mediated ubiquitin-dependent protein catabolic process was a significant biological process, with a p-value of 5.8E-21. Additionally, extracellular exosomes and protein binding were identified as significant cellular components and molecular functions, respectively. Common hub genes with degree and maximum neighborhood component (MNC) methods, including PSMD2, PSMD4, PSMA2, PSMD14, PSMD11, PSMC3, PSMC2, PSMD8, and PSMA4, were also identified. Analysis of gene expression by qRT-PCR and differential gene expression revealed that GADD45g genes can be effective genes in the proliferation of oncolytic HSV-1 virus.ConclusionThe transcriptome changes in tumor cells infected by oHSV-1 may be utilized to predict oncolytic efficacy and provide rational strategies for designing next-generation oncolytic viruses.

Dataset Information

MiRNA-Mediated Mechanisms in the Generation of Effective and Safe Oncolytic Viruses.

Publications

miRNA-Mediated Mechanisms in the Generation of Effective and Safe Oncolytic Viruses.

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