Screening and identification of miRNAs negatively regulating FAM83A/Wnt/β-catenin signaling pathway in non-small cell...

Area of Science:

• Oncology
• Molecular Biology
• Gene Regulation

Background:

• Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, often characterized by aberrant Wnt/β-catenin signaling.
• FAM83A (family with sequence similarity 83, member A) is frequently overexpressed in lung cancer, stabilizing β-catenin and activating Wnt signaling.

Purpose of the Study:

• To identify microRNAs (miRNAs) that negatively regulate FAM83A in NSCLC.
• To investigate the role of miR-1 in controlling FAM83A expression and Wnt/β-catenin pathway activity.
• To evaluate the therapeutic potential of miR-1 in NSCLC.

Main Methods:

• Screening for down-regulated miRNAs targeting FAM83A in NSCLC.
• Dual luciferase reporter assays to confirm FAM83A as a direct target of miR-1.
• Overexpression of miR-1 in NSCLC cells to assess effects on FAM83A, β-catenin, Wnt pathway genes, and cellular functions.

Main Results:

• miR-1 was identified as a direct negative regulator of FAM83A.
• Overexpression of miR-1 reduced FAM83A levels, suppressed Wnt/β-catenin signaling (decreasing AXIN2, CyclinD1, C-MYC), and inhibited β-catenin nuclear translocation.
• miR-1 overexpression promoted β-catenin degradation, inhibited NSCLC cell proliferation, migration, and invasion.

Conclusions:

• miR-1 functions as a tumor suppressor in NSCLC by targeting FAM83A and inhibiting the Wnt/β-catenin pathway.
• miR-1 demonstrates potential as a therapeutic agent for NSCLC treatment.