Exosome-derived miR-196b-5p facilitates intercellular interaction in infantile hemangioma via down-regulating CDKN1B

Though infantile hemangioma (IH) is a common benign vascular tumor, its pathogenesis remains unclear. This study explored the function of hemangioma-derived stem cells (HemSCs) derived exosomes, which exerted an intercellular effect on hemangioma-derived endothelial cells (HemECs).

First, HemSCs and HemECs were extracted and cultured. HemSCs derived exosomes (HemSCs-exos) were harvested. miRNA sequencing and target prediction were used to explore differentially expressed miRNAs and potential binding targets. After HemECs were co-cultured with HemSCs-exos, a series of in vitro assays were then performed including cell counting kit-8 (CCK-8) assay, cell apoptosis assay, cell cycle assay and tube formation assay to evaluate proliferation, angiogenesis abilities, etc. qRT-PCR and Western blot were conducted to detect the expression level of target genes and proteins.

After co-culturing with HemSCs-exos, proliferation, and angiogenesis abilities of HemECs were enhanced, while apoptosis and cell cycle arrest rate were decreased. MiR-196b-5p was observed to be significantly highly expressed in HemSCs-exos. CDKN1B was identified as the binding target of miR-196b-5p. HemECs' proliferation and angiogenesis abilities were elevated when co-cultured with exosomes from HemSCs transfected with miR-196b-5p mimic. In addition, apoptosis rate declined, and lower cells were arrested in G0/G1 phases. Cyclin E, bcl-2 were significantly highly expressed, whereas p27, Bax expression were significantly down-regulated. The positive effect of miR-196b-5p in HemSCs-exos was dramatically reversed when HemECs were transfected with oe-CDKN1B.

The current study found a novel intercellular interaction between IH cells. Briefly, exosome-derived miRNA-196b-5p in HemSCs could facilitate proliferation and angiogenesis abilities, and attenuate apoptosis and cell cycle repression rate of HemECs by directly binding with CDKN1B.