环状 RNA circCORO1C 通过调节 let-7c-5p/PBX3 轴促进喉鳞状细胞癌的进展。
Circular RNA circCORO1C promotes laryngeal squamous cell carcinoma progression by modulating the let-7c-5p/PBX3 axis.
机构信息
Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Shanxi Medical University, Taiyuan, 030001, Shanxi, People's Republic of China.
Shanxi Province Clinical Medical Research Center for Precision Medicine of Head and Neck Cancer, The First Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, People's Republic of China.
出版信息
Mol Cancer. 2020 Jun 2;19(1):99. doi: 10.1186/s12943-020-01215-4.
BACKGROUND
Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of the head and neck. LSCC patients have seriously impaired vocal, respiratory, and swallowing functions with poor prognosis. Circular RNA (circRNA) has attracted great attention in cancer research. However, the expression patterns and roles of circRNAs in LSCC remain largely unknown.
METHODS
RNA sequencing was performed on 57 pairs of LSCC and matched adjacent normal mucosa tissues to construct circRNA, miRNA, and mRNA expression profiles. RT-PCR, qPCR, Sanger sequencing, and FISH were undertaken to study the expression, localization, and clinical significance of circCORO1C in LSCC tissues and cells. The functions of circCORO1C in LSCC were investigated by RNAi-mediated knockdown, proliferation analysis, EdU staining, colony formation assay, Transwell assay, and apoptosis analysis. The regulatory mechanisms among circCORO1C, let-7c-5p, and PBX3 were investigated by luciferase assay, RNA immunoprecipitation, western blotting, and immunohistochemistry.
RESULTS
circCORO1C was highly expressed in LSCC tissues and cells, and this high expression was closely associated with the malignant progression and poor prognosis of LSCC. Knockdown of circCORO1C inhibited the proliferation, migration, invasion, and in vivo tumorigenesis of LSCC cells. Mechanistic studies revealed that circCORO1C competitively bound to let-7c-5p and prevented it from decreasing the level of PBX3, which promoted the epithelial-mesenchymal transition and finally facilitated the malignant progression of LSCC.
CONCLUSIONS
circCORO1C has an oncogenic role in LSCC progression and may serve as a novel target for LSCC therapy. circCORO1C expression has the potential to serve as a novel diagnostic and prognostic biomarker for LSCC detection.
背景
喉鳞状细胞癌（LSCC）是一种常见的头颈部恶性肿瘤。LSCC 患者的声带、呼吸和吞咽功能严重受损，预后较差。环状 RNA（circRNA）在癌症研究中受到了极大关注。然而，circRNA 在 LSCC 中的表达模式和作用仍知之甚少。
方法
对 57 对 LSCC 及配对的癌旁正常黏膜组织进行 RNA 测序，构建 circRNA、miRNA 和 mRNA 表达谱。采用 RT-PCR、qPCR、Sanger 测序和 FISH 检测 LSCC 组织和细胞中 circCORO1C 的表达、定位和临床意义。采用 RNAi 介导的敲低、增殖分析、EdU 染色、集落形成实验、Transwell 实验和凋亡分析研究 circCORO1C 在 LSCC 中的功能。通过荧光素酶报告实验、RNA 免疫沉淀、Western blot 和免疫组化研究 circCORO1C、let-7c-5p 和 PBX3 之间的调控机制。
结果
circCORO1C 在 LSCC 组织和细胞中高表达，其高表达与 LSCC 的恶性进展和不良预后密切相关。敲低 circCORO1C 抑制了 LSCC 细胞的增殖、迁移、侵袭和体内肿瘤生成。机制研究表明，circCORO1C 竞争性结合 let-7c-5p，阻止其降低 PBX3 的水平，促进上皮-间充质转化，最终促进 LSCC 的恶性进展。
结论
circCORO1C 在 LSCC 进展中具有致癌作用，可能成为 LSCC 治疗的新靶点。circCORO1C 的表达有可能成为 LSCC 检测的新型诊断和预后生物标志物。
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