Experiment Researches On The Differential Expression Of MiRNA Between Proliferative And Involuting Stages In The Same Patients With Infantile Hemangioma

Objective: Infant hemangioma is a common benign neoplasm of infancy.Although the discovery of propranolol has triggered a revolution in the treatment of infantile hemangioma,the pathogenesis of infantile hemangioma has not been fully elucidated so far.As a small non-codingRNA,microRNAs can regulate the expression of target genes by binding withRNA.In this study,microRNAs were used as the starting point to reveal the mechanism of the development of infantile hemangioma from the perspective of epigenetics.In addition,the structure of timolol maleate was modified to improve its percutaneous permeability in order to enhance the efficacy of topical medication for mixed hemangioma.Methods: From December 2017 to December 2018,the surgical specimens of infantile hemangioma patients who underwent surgical excision at the Ninth People's Hospital Affiliated to Medical College of Shanghai Jiaotong University were collected to validate the differentially expressed microRNAs using q PCR.After the validation,the lentivirus was used as the vector to construct the cell model of over-expression and inhibition of microRNAs for further study.Timolol butyrate was synthesized from timolol maleate and its percutaneous permeability was tested by skin permeation tests in vivo and in vitro.Results: Twenty-five samples were collected from different patients with infantile hemangioma in proliferative and regressive stages.The expression of miR-517c-3p was found significantly down-regulated in regressive stage.Through cell proliferation test,we found that inhibiting the function of miR517c-3p in hemangioma stem cells can significantly inhibit their proliferation.Nineteen candidate target genes of miR-517c-3p in hemangioma were predicted by bioinformatics methods.In addition,timolol butyrate was successfully synthesized from timolol maleate.The transdermal permeability of timolol butyrate was proven better than timolol maleate.Conclusion: The expression of miR-517c-3p in infantile hemangioma in involuting stage was significantly decreased,and it might lead to the inhibition of the proliferation of hemangioma stem cells,which was related to the obvious changes between the proliferative and regressive stages of infantile hemangioma.The transdermal permeability of timolol butyrate was better than that of timolol maleate.It could be used as a potential therapy for infantile hemangioma with deeper lesions.