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环状 RNA circ-TNRC6B 通过调控 miR-452-5p/DAG1 轴抑制食管鳞癌细胞的增殖和侵袭。

Circular RNA circ-TNRC6B inhibits the proliferation and invasion of esophageal squamous cell carcinoma cells by regulating the miR-452-5p/DAG1 axis.

机构信息

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.

出版信息

Mol Oncol. 2023 Jul;17(7):1437-1452. doi: 10.1002/1878-0261.13432. Epub 2023 Apr 16.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9e8/10323880/c6d8d4005c2e/MOL2-17-1437-g007.jpg

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