State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Cariology and Endodontic Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
Department of Stomatology, The Second Hospital of Shanxi Medical University, Taiyuan, China.
BMC Cancer. 2023 Jul 17;23(1):668. doi: 10.1186/s12885-023-11113-9.
Studies have shown that microRNA-191 (miR-191) is involved in the development and progression of a variety of tumors. However, the function and mechanism of miR-191 in oral squamous cell carcinoma (OSCC) have not been clarified.
The expression level of miR-191 in tumor tissues of patients with primary OSCC and OSCC cell lines were detected using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. OSCC cells were treated with miR-191 enhancers and inhibitors to investigate the effects of elevated or decreased miR-191 expression on OSCC cells proliferation, migration, cell cycle, and tumorigenesis. The target gene of miR-191 in OSCC cells were analyzed by dual-Luciferase assay, and the downstream signaling pathway of the target genes was detected using western blot assay.
The expression of miR-191 was significantly upregulated in OSCC tissues and cell lines. Upregulation of miR-191 promoted proliferation, migration, invasion, and cell cycle progression of OSCC cells, as well as tumor growth in nude mice. Meanwhile, reduced expression of miR-191 inhibited these processes. Phospholipase C delta1 (PLCD1) expression was significantly downregulated, and negatively correlated with the expression of miR-191 in OSCC tissues. Dual-Luciferase assays showed that miR-191-5p could bind to PLCD1 mRNA and regulate PLCD1 protein expression. Western blot assay showed that the miR-191 regulated the expression of β-catenin and its downstream gene through targeting PLCD1.
MicroRNA-191 regulates oral squamous cell carcinoma cells growth by targeting PLCD1 via the Wnt/β-catenin signaling pathway. Thus, miR-191 may serve as a potential target for the treatment of OSCC.
研究表明,微小 RNA-191(miR-191)参与多种肿瘤的发生发展。然而,miR-191 在口腔鳞状细胞癌(OSCC)中的功能和机制尚不清楚。
采用实时定量聚合酶链反应(RT-qPCR)和 Western blot 检测原发性 OSCC 患者肿瘤组织和 OSCC 细胞系中 miR-191 的表达水平。用 miR-191 增强子和抑制剂处理 OSCC 细胞,观察上调或下调 miR-191 表达对 OSCC 细胞增殖、迁移、细胞周期和肿瘤发生的影响。采用双荧光素酶报告基因检测分析 miR-191 在 OSCC 细胞中的靶基因,Western blot 检测靶基因下游信号通路。
miR-191 在 OSCC 组织和细胞系中的表达明显上调。上调 miR-191 促进了 OSCC 细胞的增殖、迁移、侵袭和细胞周期进程,以及裸鼠肿瘤生长。同时,下调 miR-191 抑制了这些过程。PLC 家族成员 D1(PLCD1)表达明显下调,与 OSCC 组织中 miR-191 的表达呈负相关。双荧光素酶报告基因检测显示,miR-191-5p 可与 PLCD1 mRNA 结合并调节 PLCD1 蛋白表达。Western blot 检测显示,miR-191 通过靶向 PLCD1 调控 Wnt/β-catenin 信号通路下游基因的表达。
miR-191 通过靶向 PLC 家族成员 D1(PLCD1)调控 Wnt/β-catenin 信号通路,调节口腔鳞状细胞癌细胞的生长。因此,miR-191 可能成为 OSCC 治疗的潜在靶点。