Extracellular HMGB1 promotes CD44 expression in hepatocellular carcinoma via regulating miR-21

Area of Science:

• Oncology
• Molecular Biology
• Cell Biology

Background:

• Extracellular high-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP), is implicated in hepatocellular carcinoma (HCC) progression.
• Cluster differentiation 44 (CD44) also plays a role in HCC progression, but its link with HMGB1 is not well understood.

Purpose of the Study:

• To elucidate the relationship between extracellular HMGB1 and CD44 in HCC progression.
• To investigate the underlying molecular mechanisms, including the role of miR-21 and associated signaling pathways.

Main Methods:

• Investigated the effect of extracellular HMGB1 on HCC cell invasion, sphere formation, and epithelial-mesenchymal transition (EMT).
• Analyzed the role of miR-21, CD44, OCT4/TGF-β1, and Rage/JNK signaling pathways in mediating HMGB1's effects.
• Utilized molecular biology techniques to assess gene and protein expression and pathway activation.

Main Results:

• Extracellular HMGB1 promoted HCC invasion, sphere formation, and EMT by upregulating CD44 expression, dependent on miR-21.
• miR-21 was found to upregulate CD44 expression through the activation of OCT4/TGF-β1 signaling.
• Extracellular HMGB1-induced miR-21 overexpression was mediated by the activation of Rage/JNK signaling.

Conclusions:

• Extracellular HMGB1 significantly contributes to HCC progression by enhancing miR-21/CD44 signaling.
• The Rage/JNK and OCT4/TGF-β1 pathways are crucial mediators in the HMGB1-driven HCC progression.
• Targeting the extracellular HMGB1/miR-21/CD44 axis presents a potential therapeutic strategy for HCC.