Department of Stomatology, the People's Hospital of Longhua Shenzhen, Shenzhen, Guangdong, 518109, P.R. China.
Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
Arch Oral Biol. 2020 Aug;116:104732. doi: 10.1016/j.archoralbio.2020.104732. Epub 2020 Apr 24.
The objective of this study was to explore the role of miRNAs in OSCC and to identify potential novel biomarkers or therapeutic agents in OSCC treatment.
Microarray analysis and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were performed to identify and verify differentially expressed miRNAs in OSCC tissues. The migration, invasion, proliferation and cell cycle of OSCC cells were analyzed to determine the function of miR-345 in OSCC development. Bioinformatics analysis and Dual-luciferase reporter assays were performed to identify and verify the target of miR-345.
The results showed a total of 17 miRNAs with significantly different expression in OSCC tissues (5 upregulated miRNAs and 12 downregulated miRNAs), including miR-345. The microarray results were also validated by qRT-PCR using 22 pairs of cancerous tissues and matched non-cancerous healthy samples. In particular, miR-345 expression was significantly lower in OSCC tissues. In addition, overexpression of miR-345 mimics in OSCC cells significantly inhibited their migration, invasion and proliferation while inducing cell cycle arrest in the G1 phase. Bioinformatics analysis predicted ZEB2 (zinc finger E-box-binding homeobox 2) as a potential target of miR-345, and luciferase reporter assays confirmed that miR-345 targeted ZEB2 through direct binding the 3' untranslated region of ZEB2. Furthermore, miR-345 overexpression in OSCC reduced both mRNA and protein expression of ZEB2.
The results of this study indicated that miR-345 functions as a tumor suppressor to target ZEB2 in OSCC. These findings suggest that the miR-345/ZEB2 axis may be used as a potential therapeutic target in OSCC treatment.
本研究旨在探讨 miRNA 在口腔鳞状细胞癌（OSCC）中的作用，并确定 OSCC 治疗中潜在的新型生物标志物或治疗剂。
通过微阵列分析和定量逆转录聚合酶链反应（qRT-PCR）鉴定和验证 OSCC 组织中差异表达的 miRNA。分析 OSCC 细胞的迁移、侵袭、增殖和细胞周期，以确定 miR-345 在 OSCC 发展中的功能。通过生物信息学分析和双荧光素酶报告基因实验鉴定和验证 miR-345 的靶标。
结果显示，OSCC 组织中共有 17 个 miRNA 表达差异显著（5 个上调 miRNA 和 12 个下调 miRNA），包括 miR-345。微阵列结果还通过使用 22 对癌组织和匹配的非癌健康样本的 qRT-PCR 进行了验证。特别是，miR-345 在 OSCC 组织中的表达明显降低。此外，OSCC 细胞中 miR-345 模拟物的过表达显著抑制其迁移、侵袭和增殖，同时诱导细胞周期停滞在 G1 期。生物信息学分析预测 ZEB2（锌指 E 盒结合同源盒 2）为 miR-345 的潜在靶标，荧光素酶报告基因实验证实 miR-345 通过直接结合 ZEB2 的 3'非翻译区靶向 ZEB2。此外，OSCC 中 miR-345 的过表达降低了 ZEB2 的 mRNA 和蛋白表达。
本研究结果表明，miR-345 通过靶向 ZEB2 在 OSCC 中发挥肿瘤抑制作用。这些发现表明，miR-345/ZEB2 轴可能作为 OSCC 治疗的潜在治疗靶点。
