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

Abstract

Background: 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).Methods: First, HemSCs and HemECs were extracted and cultured. HemSCs derived exosomes (HemSCsexos) 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.Results: 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. Conclusions:The current study found a novel intercellular interaction between IH cells. Briefly, exosomederived 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.

METTL3 Promotes Osteo/Odontogenic Differentiation of Stem Cells by Inhibiting miR-196b-5p Maturation

“…Some mechanisms by which miR-196b-5p regulates gene expression have been known [ 34 – 36 ]. In our previous data, we discovered that METTL3 was differentially expressed in the miR-196b-5p knockdown group and Consh group by SWATH-MS array [ 10 ].…”

Extracellular Vesicles as Delivery Shippers for Noncoding RNA‐Based Modulation of Angiogenesis: Insights from Ischemic Stroke and Cancer

“…Seventy‐six publications were found in this section, from Iran, Japan, China, Korea, and India, performed between 2013 and 2022. [ 127,174–248 ] Of these ncRNAs, 3 circRNAs, 14 lncRNAs, and 45 microRNAs were differentially expressed between healthy individuals and various cancers. Concerning circRNAs (namely, circHIPK3, circFNDC3B, and circCMTM3 derived from EVs) are upregulated and shown to regulate metatherian, tissue inhibitor of metalloproteinase 3, SOX9 through miR‐124‐3p, miR‐937‐5p, miR‐3619‐5p in breast cancer, colorectal cancer, and hepatocellular carcinoma, respectively, which enhance EC viability, migration and tube formation except in colorectal cancer to drive the process of carcinogenesis.…”

Exosomal miR-93-5p as an important driver of bladder cancer progression

“…miRNA, which is endogenous noncoding RNA 18-22 nt in length, regulates gene expression at the posttranscriptional level by binding to the 3' untranslated region (3'UTR) region of the target gene (8). A large number of studies have shown that exosome derived miRNA regulates tumor proliferation, metastasis, and angiogenesis by silencing target genes (9,10). miR-93-5p has been noted as having a critical role in the occurrence and development of many tumors and has been associated with the clinical prognosis of patients with cancer (11)(12)(13)(14).…”