Wang Xuezhong, Liu Zhiguang, Du Yalong, Hao Shuguang, Zhao Bing
Department of Thoracic Surgical Oncology Ward One, Xinxiang Central Hospital, The Fourth Clinical College of Xinxiang Medical University, Xinxiang, Henan, 453003, China.
Heliyon. 2023 Sep 9;9(9):e19807. doi: 10.1016/j.heliyon.2023.e19807. eCollection 2023 Sep.
This study aims to investigate the regulatory impact of hsa_circ_0043,603, a circular RNA, on the progression of esophageal squamous cell carcinoma (ESCC), which ranks as the sixth leading cause of global mortality. We evaluated the expression, origin, and localization of hsa_circ_0043,603 in ESCC tumors using qRT-PCR, bioinformatics, and FISH analysis. Functional studies were conducted by manipulating the hsa_circ_0043,603 expression in Eca109 cells through overexpression and silencing plasmids. Additionally, xenografts derived from circ_0043,603-overexpressing Eca109 cells enabled us to investigate tumor growth, proliferation, and apoptosis. Through Starbase analysis, we identified miR-1178-3p as a target of circ_0043,603, which was validated using RIP and luciferase assays. Furthermore, we predicted arylacetamide deacetylase (AADAC) as a target of miR-1178-3p and examined its expression in ESCC tissues using Western blot. Lastly, we performed AADAC silencing and overexpression in Eca109 cells to study their impact on cellular phenotypic features, apoptosis, and their interaction with miR-1178-3p mimics and inhibitors. The low expression of hsa_circ_0043,603 in ESCC tissue was associated with poor prognosis. Overexpression of hsa_circ_0043,603 inhibited ESCC growth, invasion, migration, and proliferation, while promoting apoptosis in vitro and suppressing tumor growth in vivo. hsa_circ_0043,603 achieved these effects by targeting the oncogenic miR-1178-3p. Furthermore, AADAC was identified as a target of miR-1178-3p, and its reduced expression was confirmed in ESCC tissues. Overexpression of AADAC in Eca109 cells resulted in suppressed cell growth, proliferation, migration, and invasion by regulating miR-1178-3p. hsa_circ_0043,603 acts as a sponge for miR-1178-3p, leading to the regulation of AADAC expression and inhibition of ESCC development. These results suggest the potential of hsa_circ_0043,603 as a therapeutic and diagnostic target for ESCC.
本研究旨在探讨环状RNA hsa_circ_0043603对食管鳞状细胞癌（ESCC）进展的调控作用，ESCC是全球第六大主要死因。我们使用qRT-PCR、生物信息学和FISH分析评估了hsa_circ_0043603在ESCC肿瘤中的表达、起源和定位。通过过表达和沉默质粒来调控Eca109细胞中hsa_circ_0043603的表达，从而进行功能研究。此外，源自过表达circ_0043603的Eca109细胞的异种移植使我们能够研究肿瘤的生长、增殖和凋亡。通过Starbase分析，我们鉴定出miR-1178-3p是circ_0043603的靶标，并使用RIP和荧光素酶测定法进行了验证。此外，我们预测芳基乙酰胺脱乙酰酶（AADAC）是miR-1178-3p的靶标，并使用蛋白质免疫印迹法检测了其在ESCC组织中的表达。最后，我们在Eca109细胞中进行了AADAC的沉默和过表达，以研究它们对细胞表型特征、凋亡的影响以及它们与miR-1178-3p模拟物和抑制剂的相互作用。hsa_circ_0043603在ESCC组织中的低表达与预后不良相关。hsa_circ_0043603的过表达在体外抑制了ESCC的生长、侵袭、迁移和增殖，同时促进了细胞凋亡，在体内抑制了肿瘤生长。hsa_circ_0043603通过靶向致癌性miR-1178-3p实现了这些作用。此外，AADAC被鉴定为miR-1178-3p的靶标，并且在ESCC组织中证实其表达降低。在Eca109细胞中过表达AADAC通过调节miR-1178-3p导致细胞生长、增殖、迁移和侵袭受到抑制。hsa_circ_0043603充当miR-1178-3p的海绵，导致AADAC表达的调节和ESCC发展的抑制。这些结果表明hsa_circ_0043603作为ESCC治疗和诊断靶标的潜力。
