MiR-181b suppresses angiogenesis by directly targeting cellular communication network factor 1

Area of Science:

• Molecular Biology
• Cell Biology
• Physiology

Background:

• Angiogenesis is crucial for physiological and pathological processes.
• MicroRNAs (miRNAs) regulate blood vessel development and angiogenesis.
• The role of miR-181b in non-tumor angiogenesis remains unclear.

Purpose of the Study:

• To investigate the role of miR-181b in angiogenesis, particularly in non-tumor contexts.
• To elucidate the molecular mechanisms underlying miR-181b's function in angiogenesis.

Main Methods:

• Assessed miR-181b expression in hypoxia-stimulated HUVECs and a mouse hindlimb ischemia (HLI) model.
• Conducted gain- and loss-of-function studies using miR-181b mimics and inhibitors in vitro.
• Evaluated the in vivo effects of miR-181b modulation on HLI recovery and Matrigel plug assays.
• Utilized reporter assays to identify direct targets of miR-181b and investigated downstream signaling pathways.

Main Results:

• miR-181b expression was downregulated in hypoxia and HLI.
• miR-181b mimic inhibited HUVEC migration and tube formation; inhibitor enhanced these processes.
• In vivo, miR-181b suppressed perfusion recovery in HLI and capillary density.
• CCN1 was identified as a direct target of miR-181b, and miR-181b inhibited angiogenesis partly via targeting CCN1 and the AMPK pathway.

Conclusions:

• miR-181b acts as a suppressor of angiogenesis.
• The miR-181b/CCN1/AMPK signaling axis is a key regulator of angiogenesis.
• Targeting miR-181b offers potential therapeutic strategies for promoting angiogenesis in non-tumor diseases.