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Hemangioma (HA) is a neoplastic disease derived from vascular endothelial cells. Recently, SASH1 has been identified as a tumor suppressor gene. The purpose of this study was to investigate the role and regulatory mechanism of SASH1 in HA. RT-PCR and Western blot were used to detect the expressions of SASH1, TRAF6 and EZH2 in HA tissues and cell lines. CCK-8, cell cycle, apoptosis, wound healing and Transwell assays were performed to evaluate the effects of SASH1 and EZH2 exerted on HA cells. The immunoprecipitation and ubiquitination assays validated the regulation of SASH1 on TRAF6 and EZH2 ubiquitination. The results showed that SASH1 and EZH2 were highly expressed in HA tissues and cell lines, while TRAF6 was downregulated. SASH1 knockdown inhibited HemECs proliferation, migration, as well as invasion, and induced G0/G1 cell cycle arrest and apoptosis, while EZH2 overexpression reversed these effects. Interestingly, the knockdown of SASH1 enhanced TRAF6 expression but suppressed EZH2 expression in HemECs. And the ubiquitination of EZH2 and TRAF6 was regulated by SASH1. Generally, SASH1 knockdown inhibited TRAF6 ubiquitination to destabilize EZH2. SASH1 may serve as a novel therapeutic target during HA progression., (Copyright © 2022. Published by Elsevier Inc.)

Hemangioma (HA) is the most common benign vascular neoplasm of infancy that is resulted from abnormal proliferation of endothelial cells. Recent studies demonstrated that long non-coding RNAs (lncRNAs) were closely related to the pathogenesis of HA. LncRNA Nuclear enriched abundant transcript 1 (NEAT1) was involved in multiple tumor formation and biological behaviors of endothelial cells. However, the role and molecular mechanism of NEAT1 in HA are still unknown. The expression levels of NEAT1 and miR-361-5p were detected in proliferating phase HAs, involuting phase HAs, and normal skin tissues. The role and mechanism of NEAT1 on the proliferation, migration and apoptosis of hemangioma endothelial cells (HemECs) were analyzed by Cell Counting Kit (CCK)-8, transwell, flow cytometry, caspase-3 activity, dual-luciferase assay, RNA immunoprecipitation, Biotin-labeled miR-361-5p pulldown assay and western blot by gain- and loss-of-functions. We found that compared with normal skin tissues, NEAT1 expression was elevated, whereas miR-361-5p decreased in HA tissues especially in proliferating phase HAs. Downregulation of NEAT1 significantly suppressed the viability, PCNA expression and migration, but increased apoptotic cell numbers and caspase-3 activity of HemECs. NEAT1 functioned as a competing endogenous RNA to regulate VEGFA expression via sponging miR-361-5p. Taken together, these findings indicate that NEAT1 promotes the proliferation and migration, whereas inhibits the apoptosis of HemECs via regulating miR-361-5p/VEGFA axis., (Copyright © 2019 Elsevier Inc. All rights reserved.)