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Authors Sun JP, Ge QX, Ren Z, Sun XF, Xie SP
Received 27 August 2018
Accepted for publication 20 November 2018
Published 28 December 2018 Volume 2019:12 Pages 309—317
DOI https://doi.org/10.2147/OTT.S185422
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Justinn Cochran
Peer reviewer comments 2
Editor who approved publication: Dr Federico Perche
Objective: Myeloid-derived
suppressor cells (MDSCs) are a heterogeneous group of cells derived from bone
marrow, which has a significant ability in inhibition of immune cell response.
In this study, the role of miR-6991-3p in regulating function of MDSCs was
investigated.
Methods: MDSCs
were isolated from different tissues of the control and hepatoma-bearing mice,
and then expression of miR-6991-3p was detected with qPCR. Then, the
miR-6991-3p mimic and inhibitor were respectively transfected into MDSCs, and
behaviors of MDSCs were evaluated, including expansion, apoptosis, and
production of inflammatory factors. Furthermore, we explored the underlying
mechanism from which miR-6991-3p regulated MDSC functions.
Results: Expression
miR-6991-3p was markedly decreased in the MDSCs derived from spleen and further
decreased in the MDSCs derived from the tumor tissue. MiR-6991-3p mimic
transfection suppressed expansion and promoted apoptosis of MDSCs, accompanied
by a significant decrease in the production of IL-6 and GM-CSF that are
identified as stimulators in MDSC expansion. In contrast, miR-6991-3p inhibitor
transfection displayed the opposite effect. miR-6991-3p bound with and
negatively regulated expression of LGALS9, a newly identified immune checkpoint
gene and activator of STAT3, suppressing production of multiple factors that
were customarily used to characterize the activation of MDSCs.
MiR-6991-3p-accommodated MDSCs displayed less suppression on T cells, while
miR-6991-3p inhibitor enhanced the suppression of MDSCs on T cells.
Conclusion: MiR-6991-3p
is identified as a novel suppressor in the expansion and activation of
myeloid-derived suppressor cells, which may be regarded as a promising target
for modulating the function of MDSCs.
Keywords: hepatoma,
myeloid-derived suppressor cells, miR-6991-3p, immunosuppression, galectin-9