IGF2-derived miR-483 mediated oncofunction by suppressing DLC-1 and associated with colorectal cancer

Area of Science:

• Molecular Oncology
• Cancer Biology

Background:

• Insulin-like growth factor 2 (IGF2) is implicated in human malignancies, including colorectal cancer (CRC).
• Hsa-miR-483 is located within the IGF2 gene, but its role in CRC pathogenesis is unclear.
• DLC-1 is a known tumor suppressor potentially involved in CRC.

Purpose of the Study:

• Investigate the IGF2-dependency of miR-483 transcription.
• Identify the functional target of miR-483.
• Evaluate the association of miR-483-3p and miR-483-5p levels with CRC in tissues and serum.

Main Methods:

• Analysis of promoter activity upstream of miR-483.
• Quantitative assessment of IGF2, miR-483-3p, and miR-483-5p expression in CRC tissues.
• Correlation analysis between IGF2 and miR-483 expression.
• Measurement of serum miR-483-5p levels in CRC patients and controls.
• Assessment of DLC-1 expression in CRC tissues and its regulation by miR-483-3p.

Main Results:

• IGF2, miR-483-3p, and miR-483-5p levels were synchronously increased in CRC tissues.
• Significant positive correlations were found between IGF2 and both miR-483-3p and miR-483-5p expression.
• Serum miR-483-5p levels were significantly higher in CRC patients compared to normal controls.
• DLC-1 expression was decreased in CRC tissues and suppressed by miR-483-3p transfection.

Conclusions:

• IGF2 may promote CRC oncogenesis partly via its parasitic miR-483, which suppresses DLC-1.
• miR-483 could be a potential therapeutic target and a biomarker for colorectal cancer detection.