title: Downregulation of miR-382 by propranolol inhibits the progression of infantile hemangioma via the PTEN-mediated AKT/mTOR pathway.
abstract: Approximately 10% of infantile hemangiomas (IHs) are the most common vascular tumors affecting children and are characterized by rapid growth, and can have destructive, disfiguring and even life-threatening consequences. Currently, propranolol is considered to be a safe and effective treatment option for problematic proliferating IHs. Recent studies have also revealed that microRNAs (miRNAs or miRs) play important roles in the regulation of angiogenesis. In this study, XPTS‑1 cells were used as a hemangioma-derived endothelial cell line constructed in our laboratory. Through a series of experiments, we discovered that miR‑382 is a novel miRNA associated with IHs, which was overexpressed in XPTS‑1 cells and was conversely downregulated by treatment with propranolol. In addition, we found that miR‑382 contributes to the progression of IHs. Our results revealed that propranolol inhibited XPTS‑1 cell migration and proliferation, and promoted apoptosis, and these effects were reversed by the restoration of miR‑382 expression by transfection of the cells with an miR‑382 overexpression vector. Further experiments revealed that the above-mentioned effects were associated with the phosphatase and tensin homolog (PTEN)-mediated AKT/mammalian target of rapamycin (mTOR) signaling pathway. The expression of PTEN was upregulated, while that of p-AKT, p-mTOR and p-p70S6K was downregulated by propranolol; these effects were partly reversed by the overexpression of miR‑382. On the whole, our study identified that the downregulation of miR‑382 by propranolol inhibits the progression of IHs via the PTEN-mediated AKT/mTOR pathway.
authors.affiliation: Department of Respiratory Medicine, The Xi'an Central Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Dongfan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Pediatric Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Pediatric Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Zhengtuan
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Pediatric Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Huaijie
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pediatric Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Weikang
authors.initials: W
authors.lastname: Pan
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006391:Hemangioma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: C555413:MIRN382 microRNA, human; D035683:MicroRNAs; D011433:Propranolol; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase