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

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Colorectal cancer (CRC) is a prevalent malignancy with poor patient prognosis, necessitating novel therapeutic strategies.
• MicroRNA (miRNA) miR-502-3p, a potential tumor suppressor, is downregulated in CRC, but its specific role and regulation remain unclear.
• Forkhead box protein O1 (FOXO1) is known to inhibit CRC cell growth, yet its influence on miR-502-3p and its downstream targets in CRC are not fully understood.

Purpose of the Study:

• To investigate the regulatory relationship between FOXO1, miR-502-3p, and cyclin-dependent kinases 6 (CDK6) in colorectal cancer.
• To determine if FOXO1 enhances miR-502-3p expression to suppress CRC cell proliferation via targeting CDK6.

Main Methods:

• Quantitative reverse transcription-PCR (qRT-PCR) and Western blot (WB) were used to assess RNA and protein levels.
• Cell Counting Kit 8 (CCK8) assay was employed to evaluate CRC cell growth.
• Dual-luciferase reporter gene (DLR) assay was utilized to confirm regulatory interactions between FOXO1, miR-502-3p, and CDK6.

Main Results:

• Both miR-502-3p and FOXO1 expression levels were found to be significantly downregulated in colorectal cancer cells.
• miR-502-3p demonstrated a suppressive effect on colorectal cancer cell proliferation.
• FOXO1 was shown to upregulate miR-502-3p expression by promoting MIR502 transcription in CRC cells.
• miR-502-3p was confirmed to inhibit CRC cell growth by directly targeting CDK6.

Conclusions:

• FOXO1 induces miR-502-3p expression, which in turn suppresses colorectal cancer cell growth by targeting CDK6.
• This newly elucidated FOXO1/miR-502-3p/CDK6 axis represents a promising therapeutic avenue for colorectal cancer treatment.