Department of Health Care, The First Affiliated Hospital of Xiamen University, Xiamen, China.
Department of Thoracic Surgery, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan, Hubei, China.
J Biochem Mol Toxicol. 2023 Nov;37(11):e23470. doi: 10.1002/jbt.23470. Epub 2023 Jul 21.
Oesophageal squamous-cell carcinoma (ESCC) is a malignant tumor of the digestive system with a poor prognosis. Recent studies have shown the promoting effect of hsa_circ_0058063 (circ_0058063) on ESCC, but the potential regulatory mechanisms of circ_0058063 in ESCC remain largely unclear. The levels of circ_0058063, microRNA-4319 (miR-4319) and mRNA of thrombospondin-1 (THBS1) were indicated by quantitative real-time polymerase chain reaction in ESCC tissues and cells. Meanwhile, the level of THBS1 was quantified by western blot analysis. In addition, the cell functions were examined by CCK8 assay, Edu assay, flow cytometry assay and transwell assay. Furthermore, the interplay between miR-4319 and circ_0058063 or THBS1 was detected by dual-luciferase reporter assay. Finally, an in vivo experiment was implemented to confirm the effect of circ_0058063. The level of circ_0058063 and THBS1 were increased, and the miR-4319 level was decreased in ESCC tissues in contrast to that in normal tissues and cells. For functional analysis, circ_0058063 deficiency inhibited cell vitality, cell proliferation, migration and invasion in ESCC cells, whereas promoted cell apoptosis. Moreover, miR-4319 was confirmed to repress the progression of ESCC cells by suppressing THBS1. In mechanism, circ_0058063 acted as a miR-4319 sponge to regulate the level of THBS1. Besides, circ_0058063 knockdown also attenuated tumour growth in vivo. Circ_0058063 facilitates the development of ESCC through increasing THBS1 expression by regulating miR-4319, which also offered an underlying targeted therapy for ESCC treatment.
食管鳞状细胞癌 (ESCC) 是一种预后较差的消化系统恶性肿瘤。最近的研究表明 hsa_circ_0058063 (circ_0058063) 对 ESCC 具有促进作用,但 circ_0058063 在 ESCC 中的潜在调节机制在很大程度上仍不清楚。通过定量实时聚合酶链反应检测 ESCC 组织和细胞中的 circ_0058063、microRNA-4319 (miR-4319) 和血栓素-1 (THBS1) mRNA 的水平。同时,通过 Western blot 分析定量 THBS1 的水平。此外,通过 CCK8 测定、Edu 测定、流式细胞术测定和 Transwell 测定检查细胞功能。此外,通过双荧光素酶报告基因测定检测 miR-4319 与 circ_0058063 或 THBS1 之间的相互作用。最后,进行了体内实验以证实 circ_0058063 的作用。与正常组织和细胞相比,ESCC 组织中的 circ_0058063 和 THBS1 水平升高,而 miR-4319 水平降低。功能分析表明,circ_0058063 缺陷抑制 ESCC 细胞的活力、细胞增殖、迁移和侵袭,而促进细胞凋亡。此外,miR-4319 通过抑制 THBS1 被证实可抑制 ESCC 细胞的进展。在机制上,circ_0058063 作为 miR-4319 的海绵来调节 THBS1 的水平。此外,circ_0058063 敲低也可在体内减弱肿瘤生长。Circ_0058063 通过调节 miR-4319 增加 THBS1 的表达促进 ESCC 的发展,这也为 ESCC 的治疗提供了潜在的靶向治疗。