Inhibition of angiogenesis by propranolol in infantile hemangiomas via lncRNA NEAT1-mediated miR-194-5p/TRAF6/NF-κB pathway.

BACKGROUND

Existing studies suggest that nuclear paraspeckle assembly transcript 1 (NEAT1) is involved in the biological behavior of endothelial cells by regulating angiogenesis. Treatment of infantile hemangioma (IH) with propranolol (Pro) has been shown to block nuclear factor-κB (NF-κB)-mediated angiogenesis. However, the underlying mechanisms remain unclear.

METHODS

RNA sequencing (RNA-Seq) was used to compare potential genes in hemangioma-derived endothelial cells (HemECs) treated with Pro to those in the control group. NEAT1 was selected. NEAT1 expression was examined via RT-qPCR. The role of NEAT1 in HemECs was analyzed using wound healing and tube formation assays. The interaction between miR-194-5p and NEAT1 or tumor necrosis factor receptor-associated factor 6 (TRAF6) was verified by dual-luciferase assay.

RESULTS

NEAT1 was elevated in proliferative tissues of IH patients. Moreover, NEAT1 knockdown suppressed the proliferation and migration of HemECs, mirroring the effects of Pro administration. Mechanistically, NEAT1 competitively binds to miR-194-5p and positively regulates the NF-κB pathway by increasing TRAF6 expression in vitro. In vivo, tumors gradually shrank following propranolol treatment, accompanied by an increase in miR-194-5p and a decrease in NEAT1, TRAF6/NF-κB pathway-related proteins, most notably in Pro plus dexamethasone.

CONCLUSION

NEAT1 regulates the TRAF6/NF-κB pathway in the pathogenesis of IH by inhibiting miR-194-5p, providing new insights for IH treatment.

IMPACT: LncRNA NEAT1 knockdown suppressed the proliferation and migration of HemECs. LncRNA NEAT1 regulates the TRAF6/ NF-κB pathways by acting as a ceRNA of miR-194-5p in vitro. LncRNA NEAT1 participates in the pathogenesis of IH and may serve as a new target for propranolol treatment.