miR-34a expands myeloid-derived suppressor cells via apoptosis inhibition
Anfei Huang1, Haitao Zhang2, Si Chen1
1Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu Province, People׳s Republic of China.
Abstract:
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population and show significant expansion under pathological conditions. microRNA plays important roles in many biological processes, whether microRNAs have a function in the expansion of MDSCs is still not very clear. In this study, miR-34a overexpression can induce the expansion of MDSCs in bone marrow chimera and transgenic mice model. The experimental results suggest that miR-34a inhibited the apoptosis of MDSCs but did not affect the proliferation of MDSCs. The distinct mRNA microarray profiles of MDSCs of wild type and miR-34a over-expressing MDSCs combined with the target prediction of miR-34a suggest that miR-34a may target genes such as p2rx7, Tia1, and plekhf1 to inhibit the apoptosis of MDSCs. Taken together, miR-34a contributes to the expansion of MDSCs by inhibiting the apoptosis of MDSCs.
Insights
MicroRNA 34a (miR-34a) promotes the expansion of myeloid-derived suppressor cells (MDSCs) by preventing their apoptosis. This study identifies miR-34a as a key regulator in MDSC expansion, offering insights into pathological conditions.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Myeloid-derived suppressor cells (MDSCs) are a diverse cell population known to expand during pathological conditions.
- The role of microRNAs (miRNAs) in MDSC expansion remains largely unclear.
Purpose of the Study:
- To investigate the function of microRNAs in the expansion of MDSCs.
- To determine the specific role of miR-34a in MDSC expansion and its underlying mechanisms.
Main Methods:
- Utilized bone marrow chimera and transgenic mice models to study miR-34a overexpression.
- Performed mRNA microarray profiling to compare gene expression between wild-type and miR-34a overexpressing MDSCs.
- Employed target prediction algorithms to identify potential miR-34a targets.
Main Results:
- Overexpression of miR-34a induced the expansion of MDSCs in vivo.
- miR-34a was found to inhibit MDSC apoptosis without affecting their proliferation.
- Potential targets of miR-34a, including p2rx7, Tia1, and plekhf1, were identified as mediators of apoptosis inhibition.
Conclusions:
- miR-34a plays a significant role in the expansion of MDSCs.
- The mechanism involves the inhibition of MDSC apoptosis, potentially through targeting specific genes.
- miR-34a is a key regulator contributing to MDSC expansion in pathological contexts.
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