Colorectal cancer (CRC) is the most common malignant tumor occurred in digestive system. However, the prognosis of CRC patients is poor. Therefore, it is urgent to illuminate the mechanism suppressing CRC and explore novel targets or therapies for CRC treatment. MicroRNAs (miRNAs) are a class of non-coding RNAs with a length of 20–23 nucleotides encoded by endogenous genes, which are associated with the development of a variety of cancers, including CRC. Studies have shown that miR-19a is identified as oncogenic miRNA and promotes the proliferation, migration and invasion of CRC cells. However, the relationship between miR-19a and ferroptosis in CRC remains unknown. Here, we reported that iron-responsive element-binding protein 2 (IREB2), as an inducer of ferroptosis, was negatively regulated by miR-19a. IREB2 is a direct target of miR-19a. In addition, ferroptosis was suppressed by miR-19a through inhibiting IREB2. Thus, we proposed a novel mechanism of ferroptosis mediated by miR-19a in CRC cells, which could give rise to a new strategy for the therapy of CRC.

Colorectal cancer (CRC) is the most common tumor of the digestive system and the third most common tumor worldwide. To date, the prognosis of CRC patients remains poor. It is urgent to identify new therapeutic targets for CRC. As a tumor suppresser, microRNA (miRNA) miR-502-5p is downregulated in CRC tissues. Nevertheless, the role of miR-502-3p in CRC is largely unclear. Besides, the transcript factor forkhead box protein O1 (FOXO1) could suppress the CRC cell growth. However, the effect of FOXO1 on miR-502-3p in CRC remains unknown. By contrast, cyclin-dependent kinases 6 (CDK6) promotes the CRC cell growth. Yet the regulatory effect of miR-502-3p on CDK6 in CRC has not been reported. Thus, the primary aim of this study was to investigate whether FOXO1 enhanced miR-502-3p expression to suppress the CRC cell growth by targeting CDK6. Here, RNA level and protein level were detected by quantitative reverse transcription-PCR (qRT-PCR) and western blot (WB), respectively. Besides, the cell growth was detected by Cell Counting Kit 8 (CCK8) assay. Moreover, the regulatory effect of FOXO1 on miR-502-3p or miR-502-3p on CDK6 was determined using dual-luciferase reporter gene (DLR) assay. Results revealed that miR-502-3p and FOXO1 were downregulated in CRC cells. Besides, miR-502-3p suppressed the CRC cell growth. Moreover, FOXO1 could increase the miR-502-3p level through facilitating MIR502 transcription in CRC cells. In addition, miR-502-3p could suppress the CRC cell growth by targeting CDK6. These findings indicated that FOXO1 induced miR-502-3p expression to suppress the CRC cell growth through targeting CDK6, which might provide new therapeutic targets for CRC.