MiR- 150 deletion promotes lung tumor growth by upregulating P-STAT3 and ROS in MDSCs

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Lung cancer is a leading global malignancy.
• Myeloid-derived suppressor cells (MDSCs) are key regulators of the lung tumor microenvironment.
• MicroRNAs (miRNAs) play a critical role in modulating MDSC function and tumor progression.

Purpose of the Study:

• To investigate the specific role of miR-150 in regulating MDSCs within the context of lung tumors.
• To elucidate the molecular mechanisms by which miR-150 influences lung tumor growth and MDSC activity.

Main Methods:

• Establishment of lung tumor models using miR-150 knockout (KO) mice and LLC cell inoculation.
• Analysis of MDSC populations, serum cytokine levels (IL-6, G-CSF), and suppressive molecule expression in tumors.
• In vitro assessment of reactive oxygen species (ROS), IRE1α, and P-STAT3 expression in MDSCs upon miR-150 inhibition.
• In vivo evaluation of STAT3 inhibitor efficacy on tumor growth and ROS levels in miR-150 KO mice.

Main Results:

• miR-150 deletion significantly promoted lung tumor growth and increased MDSC infiltration.
• Knockdown of miR-150 led to elevated serum IL-6 and G-CSF levels and enhanced MDSC suppressive function.
• Inhibition of miR-150 in vitro increased ROS, IRE1α, and P-STAT3 expression in MDSCs.
• In vivo administration of a STAT3 inhibitor markedly suppressed tumor growth and reduced ROS in MDSCs of miR-150 KO mice.

Conclusions:

• miR-150 deletion promotes lung tumor progression by upregulating P-STAT3 and ROS in MDSCs.
• STAT3 signaling is a critical pathway mediating the effects of miR-150 deficiency on MDSCs and tumor growth.
• Targeting STAT3 represents a potential therapeutic strategy to counteract the pro-tumorigenic effects of miR-150 loss in lung cancer.