Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infantile hemangioma is the most common vascular tumor affecting infants, which is associated with clonal expansion of endothelial cells. The aim of this study is to determine the role of microRNA (miR)-143 in the growth and survival of hemangioma-derived endothelial cells (HemECs). We examined the expression of miR-143 in patients with proliferating-phase (n=10) and involuting-phase (n=8) hemangiomas. The effects of ectopic expression of miR-143 on the viability, proliferation, cell cycle distribution, and apoptosis of HemECs were explored. We also identified the target gene(s) that was involved in the activity of miR-143. It was found that proliferating hemangiomas had significantly (P<0.05) lower levels of miR-143 than involuting counterparts. Reexpression of miR-143 significantly reduced the viability and proliferation of HemECs, while knockdown of miR-143 led to an increase in the proliferation of HemECs. Moreover, overexpression of miR-143 arrested HemECs at the G0/G1 phase and promoted caspase-3-dependent apoptosis. At the molecular level, miR-143 overexpression significantly promoted the expression of p21 and p53 and reduced the expression of cyclin D1, CDK2, CDK4, and Bcl-2. Silencing of Bcl-2 phenocopied the effect of miR-143 overexpression on the proliferation and apoptosis of HemECs. Furthermore, co-expression of Bcl-2 reversed the growth-suppressive effect of miR-143 on HemECs. Taken together, miR-143 acts as a suppressor in the growth of HemECs, at least partially, through downregulation of Bcl-2. Reexpression of miR-143 may represent a potential therapeutic strategy for the treatment of proliferating hemangiomas.
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PMID:microRNA-143 acts as a suppressor of hemangioma growth by targeting Bcl-2. 2871 10

Infantile hemangioma is the most common soft tissue tumors in childhood. In clinic, propranolol is widely used for infantile hemangioma therapy. However, some of the infantile hemangioma patients display resistance to propranolol treatment. Previous studies show that miR-187-3p is inhibited in hepatocellular carcinoma and lung cancer, while the role of miR-187-3p in infantile hemangioma remains unclear. In the present study, we explore the biological role of miR-187-3p in infantile hemangioma. The mRNA and protein levels of related genes were detected by real-time PCR and Western blotting. CCK8 assay was used to detect cell viability and IC50 values of propranolol. Cell apoptosis was detected by Caspase-3 Activity assay. Luciferase reporter assay and biotin RNA pull down assay were used to detect the interaction between miR-187-3p and the targeted gene. MiR-187-3p was down-regulated in infantile hemangioma tissues and promoted propranolol sensitivity of HemSCs. Mechanically, NIPBL was the direct target of miR-187-3p in HemSCs. NIPBL downregulation inhibited propranolol resistance of HemSCs. Re-introduction of NIPBL reversed miR-187-3p-meidated higher propranolol sensitivity of HemSCs. MiR-187-3p enhanced propranolol sensitivity of hemangioma stem cells via targeting NIPBL. MiR-187-3p may serve as a novel prognostic indicator and potential target for infantile hemangioma therapy.Key words: MiR-187-3p, infantile hemangioma, propranolol, resistance, NIPBL.
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PMID:MiR-187-3p Enhances Propranolol Sensitivity of Hemangioma Stem Cells. 3071 20