Exosomal MiR-423-3p inhibits macrophage M2 polarization to suppress the malignant progression of cervical cancer

Abstract

Background: Cervical cancer (CC) is the leading cause of death among women-related cancers. MicroRNAs (miRNAs) exerting important impacts in the development of CC is widely recognized. MiR-423-3p was found to be with low expression in the plasma exosomes of patients with CC. Exo-miRNAs have been documented to be potential modulators of cancer progression, and exosomes have been reported to be associated with macrophage polarization.

Aim: We aim to verify the potential function exosomal miR-423-3p may exert in CC cells as well as its underlying mechanism.

Methods: A co-culture model of exosomes and CC cells was established and the function of exosomal miR-423-3p was verified through Transwell, colony formation and other assays. A co-culture model of exosomes and macrophages, together with mechanism experiments in vitro and in vivo was taken to verify the molecular mechanism of exosomal miR-423-3p in CC.

Results: Exosomal miR-423-3p inhibited macrophage M2 polarization so as to suppress CC cell progression as well as tumor growth. MiR-423-3p regulated macrophage M2 polarization by targeting cyclin-dependent kinase 4 (CDK4) mRNA, and it inhibited the phosphorylation of signal transducer and activator of transcription 3 (STAT3) via CDK4 to silence Interleukin 6 (IL-6) expression.

Conclusion: Exosomal miR-423-3p inhibited macrophage M2 polarization to suppress the progression of CC cells.

Keywords: CDK4; Cervical cancer; M2 polarization; MiR-423–3p; STAT3.