Research Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
The Third Department of Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Mol Oncol. 2023 Jul;17(7):1437-1452. doi: 10.1002/1878-0261.13432. Epub 2023 Apr 16.
Previous studies have uncovered the key role of circular RNAs (circRNAs) in various diseases, including cancer. However, the growth-inhibitory effects of circRNAs on esophageal squamous cell carcinoma (ESCC) have not been completely elucidated. This study characterized a newly identified circRNA derived from exons 9-13 of TNRC6B (named circ-TNRC6B). The expression of circ-TNRC6B in ESCC tissues was markedly downregulated when compared to that in non-tumor tissues. In 53 ESCC cases, circ-TNRC6B expression was negatively correlated with the T stage. Multivariate Cox regression analysis showed that circ-TNRC6B upregulation was an independent protective factor for ESCC patients' prognosis. Overexpression and knockdown functional experiments demonstrated that circ-TNRC6B inhibited ESCC cell proliferation, migration, and invasion. RNA immunoprecipitation and dual-luciferase reporter assays demonstrated that circ-TNRC6B sponges oncogenic miR-452-5p to upregulate the expression and activity of DAG1. Treatment with miR-452-5p inhibitor partially reversed the circ-TNRC6B-induced changes in the biological behavior of ESCC cells. These findings demonstrated that circ-TNRC6B exerts a tumor-suppressing effect in ESCC through the miR-452-5p/DAG1 axis. Thus, circ-TNRC6B is a potential prognostic biomarker for the clinical management of ESCC.
先前的研究已经揭示了环状 RNA（circRNAs）在各种疾病中的关键作用，包括癌症。然而，circRNAs 对食管鳞状细胞癌（ESCC）的生长抑制作用尚未完全阐明。本研究描述了一种新鉴定的来自 TNRC6B 外显子 9-13 的 circRNA（命名为 circ-TNRC6B）。与非肿瘤组织相比，circ-TNRC6B 在 ESCC 组织中的表达明显下调。在 53 例 ESCC 病例中，circ-TNRC6B 的表达与 T 分期呈负相关。多变量 Cox 回归分析表明，circ-TNRC6B 的上调是 ESCC 患者预后的独立保护因素。过表达和敲低功能实验表明，circ-TNRC6B 抑制 ESCC 细胞的增殖、迁移和侵袭。RNA 免疫沉淀和双荧光素酶报告基因实验表明，circ-TNRC6B 作为竞争性内源性 RNA （ceRNA），可以吸附致癌 miR-452-5p，从而上调 DAG1 的表达和活性。用 miR-452-5p 抑制剂处理部分逆转了 circ-TNRC6B 诱导的 ESCC 细胞生物学行为的变化。这些发现表明，circ-TNRC6B 通过 miR-452-5p/DAG1 轴在 ESCC 中发挥抑癌作用。因此，circ-TNRC6B 是 ESCC 临床管理中一种有潜力的预后生物标志物。
