Exosomal miR-143-3p released from cancer cells suppresses cervical cancer progression and promotes ferroptosis through directly targeting KLF5.

Cervical cancer is the most prevalent gynecological malignancy. Tumor-derived exosomal microRNAs (miRNAs) have been increasingly considered important players in cervical cancer; however, the specific function and molecular mechanism of exosomal miR-143-3p in cervical cancer are unclear. MiR-143-3p and Kruppel-like factor 5 (KLF5) expression were detected using CancerMIRNome, UALCAN, RT-qPCR, and immunoblotting. The cargo information of miR-143-3p was obtained in ExoCarta, and cervical cancer cell-derived exosomes were identified and characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and immunoblotting. CCK-8 and EDU assays were used to detect cell proliferation, while wound healing and Transwell assays were used to detect cell migration and invasion, respectively. TargetScan and luciferase reporter assays were used to predict and test the interaction between miR-143-3p and KLF5. Assay kits were used to measure glutathione (GSH), malondialdehyde (MDA), and reactive oxygen species (ROS) levels. Tumor growth, metastasis, and cervical damage were detected in cervical cancer-bearing mice. Here, miR-143-3p was lowly expressed in cervical cancer tissues and cells and was highly enriched in cervical cancer-derived exosomes. MiR-143-3p mimic inhibited proliferation, migration, and invasion, and induced cell-cycle arrest of cervical cancer cells. MiR-143-3p targeted and downregulated KLF5. KLF5 was overexpressed in cervical cancer, and its silencing suppressed the proliferation, migration, and invasion of cervical cancer cells. Moreover, KLF5 deficiency drove ferroptosis; KLF5 overexpression reversed the impacts of miR-143-3p on tumor growth and metastasis in cervical cancer both in vitro and in vivo. Our work underscored that miR-143-3p, carried and transferred by cervical cancer cell-derived exosomes, plays an anti-oncogenic role in cervical cancer via KLF5.