Myofibroblast-Specific Msi2 Knockout Inhibits HCC Progression in a Mouse Model

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Myofibroblasts are crucial in hepatocellular carcinoma (HCC) development and progression.
• Musashi RNA binding protein 2 (MSI2) is highly expressed in peritumoral myofibroblasts in HCC patients.

Purpose of the Study:

• To investigate the role and mechanism of myofibroblast MSI2 in HCC progression.
• To explore MSI2 as a potential therapeutic target in HCC.

Main Methods:

• Assessed myofibroblast infiltration and collagen deposition in 117 HCC patient tissues.
• Generated a myofibroblast-specific Msi2 knockout mouse model (Msi2ΔCol1a1).
• Orthotopically transplanted mouse HCC cells into knockout and control mice.

Main Results:

• Myofibroblast-derived collagen deposition correlated with poor HCC prognosis.
• Myofibroblast-specific Msi2 deletion significantly inhibited HCC growth, reduced metastasis, and improved survival (P=0.002).
• Msi2 deletion in myofibroblasts reversed their pro-tumorigenic effects on HCC cells, including proliferation, invasion, and EMT, by reducing IL-6/IL-11 secretion via the ERK1/2 pathway.

Conclusions:

• Myofibroblast-specific Msi2 knockout abrogates tumor-promoting functions and inhibits HCC progression in vivo.
• Targeting myofibroblast MSI2 represents a promising therapeutic strategy for HCC treatment.