PloS one · 2024
MiR-27a inhibits the growth and metastasis of multiple myeloma through regulating Th17/Treg balance.
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Lu Weiguo, Huang Hui, Xu Zhanjie, Xu Shumin, Zhao Kewei, Xiao Mingfeng
Аннотация
BACKGROUND: The imbalance between T helper 17 (Th17) and T regulatory (Treg) cells plays a key role in the progression of multiple myeloma (MM).
METHODS: The gene expression profiles of MM were acquired and examined from the Gene Expression Omnibus (GEO) database (GSE72213). Our research involved experimental investigations conducted using the MOPC-MM mouse model. Dysregulation of Treg and Th17 cells was evaluated through flow cytometry, while the levels of inflammatory factors were measured using the enzyme-linked immunosorbent assay. Cell proliferation was gauged using the Cell Counting Kit-8 assay, and cell apoptosis was quantified via flow cytometry. Cell metastasis capabilities were determined by conducting transwell assays. To confirm the relationship between miR-27a and PI3K, a dual-luciferase reporter assay was employed. Finally, proteins associated with the PI3K/AKT/mTOR signaling pathway were assessed using western blotting.
RESULTS: MiR-27a exhibited reduced expression levels in MM. Moreover, it exerted control over the equilibrium of Th17 and Treg cells while reducing the expression of inflammatory mediators such as TGF-β1 and IL-10 in an in vivo setting. Elevated miR-27a levels led to the inhibition of cell viability, colony formation capacity, migratory and invasive traits in an in vitro context. The PI3K/AKT/mTOR signaling pathway was identified as a direct target of miR-27a and could reverse the effects induced by miR-27a in MM cells. Notably, PI3K was directly targeted by miR-27a.
CONCLUSIONS: Our study revealed that miR-27a inhibited MM evolution by regulating the Th17/Treg balance. Inhibition of the PI3K/AKT/mTOR signaling pathway by miR-27a may play a potential mechanistic role.
METHODS: The gene expression profiles of MM were acquired and examined from the Gene Expression Omnibus (GEO) database (GSE72213). Our research involved experimental investigations conducted using the MOPC-MM mouse model. Dysregulation of Treg and Th17 cells was evaluated through flow cytometry, while the levels of inflammatory factors were measured using the enzyme-linked immunosorbent assay. Cell proliferation was gauged using the Cell Counting Kit-8 assay, and cell apoptosis was quantified via flow cytometry. Cell metastasis capabilities were determined by conducting transwell assays. To confirm the relationship between miR-27a and PI3K, a dual-luciferase reporter assay was employed. Finally, proteins associated with the PI3K/AKT/mTOR signaling pathway were assessed using western blotting.
RESULTS: MiR-27a exhibited reduced expression levels in MM. Moreover, it exerted control over the equilibrium of Th17 and Treg cells while reducing the expression of inflammatory mediators such as TGF-β1 and IL-10 in an in vivo setting. Elevated miR-27a levels led to the inhibition of cell viability, colony formation capacity, migratory and invasive traits in an in vitro context. The PI3K/AKT/mTOR signaling pathway was identified as a direct target of miR-27a and could reverse the effects induced by miR-27a in MM cells. Notably, PI3K was directly targeted by miR-27a.
CONCLUSIONS: Our study revealed that miR-27a inhibited MM evolution by regulating the Th17/Treg balance. Inhibition of the PI3K/AKT/mTOR signaling pathway by miR-27a may play a potential mechanistic role.