Department of Thoracic Surgery, The First Affiliated Hospital of China Medical University, He-Ping, Shen-Yang 110001, Liao-Ning Province, China.
Aging (Albany NY). 2021 Jan 27;13(8):12179-12193. doi: 10.18632/aging.103071.
The abnormal expression and regulation of circular RNA (circRNA) is involved in the occurrence and development of a variety of tumors. The current study aimed to determine the role of circRNA_141539 in esophageal squamous cell carcinoma (ESCC). CircRNA_141539 expression in ESCC was detected via circRNA chip analysis and verified via reverse transcription-quantitative PCR. Associations between circRNA_141539, patient clinicopathological characteristics and prognosis were also statistically analyzed. Additionally, the effects of circRNA_141539 on ESCC cell proliferation and invasion were assessed. A dual-luciferase assay was performed to analyze the interaction between circRNAs, microRNAs (miRs) and mRNAs. The results revealed that circRNA_141539 was significantly up-regulated in patients with ESCC. Furthermore, high circRNA_141539 expressions were significantly associated with TNM stage, differentiation and poor prognosis, revealing high diagnostic value (P<0.05). Furthermore, circRNA_141539 overexpression promoted cell proliferation and invasion, while circRNA_141539 silencing inhibited cell proliferation and invasion (P<0.05). The dual-luciferase reporter assay identified that circRNA_141539 directly binds to miR-4469 and also revealed that cyclin-dependent kinase-3 (CDK3) was negatively regulated by miR-4469. The results indicated that circRNA_141539 served as an oncogenic factor in ESCC by sponging miR-4469 and activating CDK3 expression. circRNA_141539 may present as a novel diagnostic and prognostic biomarker and a therapeutic target for patients with ESCC.
环状 RNA(circRNA)的异常表达和调控与多种肿瘤的发生和发展有关。本研究旨在探讨 circRNA_141539 在食管鳞状细胞癌(ESCC)中的作用。通过 circRNA 芯片分析检测 ESCC 中 circRNA_141539 的表达,并通过逆转录定量 PCR 进行验证。还对 circRNA_141539 与患者临床病理特征和预后的相关性进行了统计学分析。此外,还评估了 circRNA_141539 对 ESCC 细胞增殖和侵袭的影响。通过双荧光素酶报告实验分析 circRNAs、microRNAs(miRs)和 mRNAs 之间的相互作用。结果表明,circRNA_141539 在 ESCC 患者中显著上调。此外,高 circRNA_141539 表达与 TNM 分期、分化和不良预后显著相关,具有较高的诊断价值(P<0.05)。此外,circRNA_141539 的过表达促进了细胞增殖和侵袭,而 circRNA_141539 的沉默抑制了细胞增殖和侵袭(P<0.05)。双荧光素酶报告实验鉴定出 circRNA_141539 可直接与 miR-4469 结合,并发现 cyclin-dependent kinase-3(CDK3)受 miR-4469 的负调控。结果表明,circRNA_141539 通过海绵 miR-4469 并激活 CDK3 表达,在 ESCC 中充当致癌因子。circRNA_141539 可能成为 ESCC 患者的新型诊断和预后生物标志物及治疗靶点。