Halofuginone Affects the miR-34c-5p/MAP2K1 Axis Involved in the Development of Colorectal Cancer

Area of Science:

• Molecular oncology
• Cancer epigenetics
• MicroRNA therapeutics

Background:

• Colorectal cancer (CRC) is a heterogeneous disease driven by genetic and epigenetic changes.
• MicroRNAs (miRNAs) play crucial roles in CRC development, including epithelial-mesenchymal transition (EMT), proliferation, migration, and metastasis.
• The precise mechanisms underlying miRNA involvement in CRC remain incompletely understood.

Purpose of the Study:

• To identify CRC-associated differentially expressed miRNAs, focusing on miR-34c-5p.
• To validate miR-34c-5p's direct target and elucidate its regulatory mechanism in CRC.
• To investigate the therapeutic potential of halofuginone (HF) via the miR-34c-5p/MAP2K1 axis in CRC.

Main Methods:

• Differential miRNA expression profiling using miRNA sequencing (miRNA-Seq) and validation via RT-qPCR.
• In vitro and in vivo assessment of miR-34c-5p's functional impact on CRC cell behaviors.
• Dual-luciferase reporter assays for target validation and immunohistochemistry (IHC) for MAP2K1 analysis in clinical samples.

Main Results:

• miR-34c-5p was significantly downregulated in CRC cells and suppressed malignant behaviors both in vitro and in vivo.
• MAP2K1 was confirmed as a direct target of miR-34c-5p, with its expression positively correlating with colorectal precancerous lesion severity.
• Halofuginone (HF) treatment suppressed CRC progression by upregulating miR-34c-5p and downregulating MAP2K1.

Conclusions:

• The miR-34c-5p/MAP2K1 axis is integral to colorectal cancer progression.
• Halofuginone exerts anti-tumor effects by modulating the miR-34c-5p/MAP2K1 pathway.
• The miR-34c-5p/MAP2K1 axis represents a promising therapeutic target for CRC prevention and treatment.