Unraveling The Effects of DICER1 Overexpression on Immune-Related Genes Expression in Mesenchymal Stromal/Stem Cells: Insights for Therapeutic Applications

Overview

Journal Cell J

Specialty Cell Biology

Date 2023 Oct 22

PMID 37865878

Authors

Hamid Reza Bidkhori

Moein Farshchian

Halimeh Hasanzadeh

Reza Jafarzadeh Esfehani

Reihaneh Alsadat Mahmoudian

Mahdi Moradi Marjaneh

Houshang Rafatpanah

Affiliations

Soon will be listed here.

Abstract

Objective: The immunoregulatory properties of mesenchymal stromal/stem cells (MSCs) bring a promise for the treatment of inflammatory diseases. However, their ability to suppress the immune system is unstable. To enhance their effectiveness against immune responses, it may be necessary to manipulate MSCs. Although some dsRNA transcripts come from invading viruses, the majority of dsRNA has an endogenous origin and is known as endo-siRNA. DICER1 is a ribonuclease protein that can generate small RNAs to modulate gene expression at the post-transcriptional level. We aimed to evaluate the expression of several immune-related genes at mRNA and protein levels in MSCs overexpressing DICER1 exogenously.

Materials And Methods: In this comparative transcriptomic experimental study, the adipose-derived MSCs (Ad-MSCs) were transfected using the pCAGGS-Flag-hsDicer vector for the overexpression. Following the RNA extraction, mRNA expression level of and several inflammatory cytokines were examined. We performed a relative real-time polymerase chain reaction (PCR) assay and transcriptome analysis between two groups including DICER1- transfected MSCs and control MSCs. Moreover, media from the transfected MSCs were evaluated for various interferon response factors by ELISA.

Results: The overexpression of is associated with a significant increase in the mRNA expression level of and genes and a downregulation of the TSG-6 gene in MSCs. Moreover, the expression levels of and were higher in the DICER1-transfected MSCs group.

Conclusion: It seems that the ectopic expression of DICER1 in Ad-MSCs is linked to alterations in the expression level of immune-related genes. It is suggested that the manipulation of immune-related pathways in MSCs via the Dicer1 overexpression could facilitate the development of MSCs with distinct immunoregulatory phenotypes.

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