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FOXO1-Induced miR-502-3p Suppresses Colorectal Cancer Cell Growth through Targeting CDK6

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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… Click to show full abstract

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.

Keywords: foxo1; crc; cell growth; mir 502

Journal Title: Journal of Oncology
Year Published: 2023

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