Department of Plastic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang City 453100, Henan, China.
Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City 450052, Henan, China.
Burns. 2023 Sep;49(6):1392-1402. doi: 10.1016/j.burns.2022.12.014. Epub 2022 Dec 30.
Keloids (KD) are benign fibroproliferative tumors and circular RNAs (circRNAs) may participate in KD progression. At present, whether circ_0008450 regulates keloid-derived fibroblast phenotypes remains unclear. This study aimed to explore the functions of circ_0008450 in keloid (KD)-derived fibroblast phenotypes and the underlying mechanism.
Quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay was performed to determine the expression of circ_0008450, miR-1224-5p, insulin like growth factor binding protein 5 (IGFBP5) and extracellular matrix (ECM)-related markers. 5-Ethynyl-2'-deoxyuridine (EdU) assay was conducted to assess cell proliferation ability. Flow cytometry analysis was used to analyze cell cycle and cell apoptosis. Scratch assay and transwell assay were utilized to examine cell migration and invasion. Mechanism assays were executed to verify the relations of circ_0008450, miR-1224-5p and IGFBP5.
Circ_0008450 was highly expressed in KD tissues and KD-derived fibroblasts. Circ_0008450 silencing inhibited KD-derived fibroblast proliferation, cell cycle, and motility and promoted apoptosis. The effect of circ_0008450 knockdown on KD-derived fibroblast processes was ameliorated by miR-1224-5p downregulation. IGFBP5 was a target gene of miR-1224-5p. IGFBP5 upregulation abated miR-1224-5p-mediated effects on KD-derived fibroblast processes.
Circ_0008450 promoted KD-derived fibroblast proliferation, migration, and invasion and repressed apoptosis via sponging miR-1224-5p and elevating IGFBP5.
瘢痕疙瘩（KD）是良性的纤维增生性肿瘤，环状 RNA（circRNA）可能参与 KD 的进展。目前，circ_0008450 是否调节瘢痕疙瘩衍生的成纤维细胞表型尚不清楚。本研究旨在探讨 circ_0008450 在瘢痕疙瘩（KD）衍生的成纤维细胞表型中的作用及其潜在机制。
采用实时定量聚合酶链反应（qRT-PCR）或 Western blot 检测 circ_0008450、miR-1224-5p、胰岛素样生长因子结合蛋白 5（IGFBP5）和细胞外基质（ECM）相关标志物的表达。5-乙炔基-2'-脱氧尿苷（EdU）检测评估细胞增殖能力。流式细胞术分析用于分析细胞周期和细胞凋亡。划痕实验和 Transwell 实验用于检测细胞迁移和侵袭。机制实验验证 circ_0008450、miR-1224-5p 和 IGFBP5 之间的关系。
circ_0008450 在 KD 组织和 KD 衍生的成纤维细胞中高表达。circ_0008450 沉默抑制 KD 衍生的成纤维细胞增殖、细胞周期和运动，并促进细胞凋亡。miR-1224-5p 下调可减轻 circ_0008450 敲低对 KD 衍生的成纤维细胞过程的影响。IGFBP5 是 miR-1224-5p 的靶基因。IGFBP5 的上调减轻了 miR-1224-5p 介导的对 KD 衍生的成纤维细胞过程的影响。
circ_0008450 通过海绵吸附 miR-1224-5p 和上调 IGFBP5 促进 KD 衍生的成纤维细胞增殖、迁移和侵袭，并抑制细胞凋亡。
