Wu Maosong, Tang Yongsheng, Hu Gang, Yang Chunjian, Ye Kaichuang, Liu Xianluo
Department of General Surgery, The Second People's Hospital of Hefei, Hefei, Anhui 230011, P.R. China.
Department of Vascular Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 230011, P.R. China.
Exp Ther Med. 2020 Apr;19(4):3017-3023. doi: 10.3892/etm.2020.8546. Epub 2020 Feb 25.
Hemangiomas (HAs) are benign neoplasms of the vasculature. MicroRNA-4458 (miR-4458) has been reported to function as a tumor suppressor in multiple malignancies, but its biological function in HAs remains unknown. In the present study, the potential role of miR-4458 in HA-derived endothelial cells (HDECs) was investigated. Firstly, reverse-transcription-quantitative PCR analysis was used to confirm the expression of miR-4458 in HDECs following transfection with miR-4458 mimics or inhibitor. Subsequently, MTT and EdU assays were performed and subsequently determined that miR-4458 overexpression significantly inhibited proliferation, and knockdown promoted cell proliferation in HDECs. Flow cytometry analysis revealed that miR-4458 overexpression induced cell cycle arrest, whereas knockdown reversed G0/G1 phase arrest and apoptosis. Furthermore, insulin-like growth factor 1 receptor (IGF1R) was identified as a target of miR-4458. IGF1R knockdown enhanced the effects of miR-4458 on cell proliferation, cell cycle G0/G1 phase arrest and apoptosis in HDECs. Taken together, the results revealed that miR-4458 targeting of IGF1R may serve as a novel therapeutic strategy for treating patients with HAs.
血管瘤(HAs)是脉管系统的良性肿瘤。据报道,微小RNA-4458(miR-4458)在多种恶性肿瘤中发挥肿瘤抑制作用,但其在血管瘤中的生物学功能尚不清楚。在本研究中,研究了miR-4458在血管瘤来源的内皮细胞(HDECs)中的潜在作用。首先,采用逆转录定量PCR分析来确认用miR-4458模拟物或抑制剂转染后HDECs中miR-4458的表达。随后,进行MTT和EdU测定,随后确定miR-4458过表达显著抑制增殖,而敲低则促进HDECs中的细胞增殖。流式细胞术分析显示,miR-4458过表达诱导细胞周期停滞,而敲低则逆转G0/G1期停滞和凋亡。此外,胰岛素样生长因子1受体(IGF1R)被确定为miR-4458的一个靶点。IGF1R敲低增强了miR-4458对HDECs细胞增殖、细胞周期G0/G1期停滞和凋亡的影响。综上所述,结果表明miR-4458靶向IGF1R可能成为治疗血管瘤患者的一种新的治疗策略。