Department of Stomatology, Hospital of 363, Chengdu, China.
Department of Orthodontics, Hospital of Stomatology, Southwest Medical University, Luzhou, China.
Neoplasma. 2020 May;67(3):528-536. doi: 10.4149/neo_2020_190703N582. Epub 2020 Feb 17.
Oral squamous cell carcinoma (OSCC) is the most common human malignancy worldwide with a high mortality rate. MiR-769-5p has been reported to be downregulated in tissues and blood of OSCC patients. However, the exact roles and pathogenesis of miR-769-5p involved in OSCC remain unclear. The expressions of miR-769-5p and Janus kinase (JAK1) in OSCC tissues and cells were assessed by RT-qPCR and western blot assay. Expressions of apoptotic-related (Bcl-2, Bax, and cleaved-caspase 3) and EMT-associated proteins (MMP9, E-cadherin, N-cadherin, and Vimentin) were detected by western blot assay. The effect of miR-769-5p and JAK1 on proliferation, migration, invasion, and apoptosis was evaluated by CCK-8, transwell, and flow cytometry assays, respectively. The binding interaction of miR-769-5p and JAK1 were predicted by TargetScan and demonstrated by dual-luciferase reporter assays. The volume and weight of the tumor were measured in the subcutaneous transplantation experiment. MiR-769-5p was downregulated, and JAK1 was upregulated in OSCC tissues and cells. MiR-769-5p restrained Bcl-2, MMP9, N-cadherin, and Vimentin protein level and accelerated Bax, cleaved-caspase 3 and E-cadherin protein level, while JAK1 partly overturned these effects. Also, miR-769-5p suppressed proliferation, migration, invasion, and increased apoptosis of OSCC, while the reintroduction of JAK1 abolished these effects. Moreover, JAK1 was verified to be the target of miR-769-5p. In addition, miR-769-5p inhibited the development of OSCC cells in vivo. These results indicate that miR-769-5p suppressed OSCC cell development via targeting the JAK1/STAT3 pathway, providing an underlying therapeutic method for OSCC.
口腔鳞状细胞癌（OSCC）是全球最常见的人类恶性肿瘤，死亡率较高。已有报道称，miR-769-5p 在 OSCC 患者的组织和血液中表达下调。然而，miR-769-5p 参与 OSCC 的确切作用和发病机制仍不清楚。通过 RT-qPCR 和 Western blot 检测 OSCC 组织和细胞中 miR-769-5p 和 Janus 激酶（JAK1）的表达。通过 Western blot 检测凋亡相关（Bcl-2、Bax 和 cleaved-caspase 3）和 EMT 相关蛋白（MMP9、E-钙粘蛋白、N-钙粘蛋白和波形蛋白）的表达。通过 CCK-8、Transwell 和流式细胞术分别评估 miR-769-5p 和 JAK1 对增殖、迁移、侵袭和凋亡的影响。通过 TargetScan 预测 miR-769-5p 和 JAK1 的结合相互作用，并通过双荧光素酶报告基因实验进行验证。在皮下移植实验中测量肿瘤的体积和重量。miR-769-5p 在 OSCC 组织和细胞中下调，而 JAK1 上调。miR-769-5p 抑制 Bcl-2、MMP9、N-钙粘蛋白和波形蛋白蛋白水平，加速 Bax、cleaved-caspase 3 和 E-钙粘蛋白蛋白水平，而 JAK1 部分逆转了这些作用。此外，miR-769-5p 抑制 OSCC 的增殖、迁移、侵袭，并增加其凋亡，而 JAK1 的再引入则消除了这些作用。此外，JAK1 被验证为 miR-769-5p 的靶标。此外，miR-769-5p 抑制了体内 OSCC 细胞的发展。这些结果表明，miR-769-5p 通过靶向 JAK1/STAT3 通路抑制 OSCC 细胞的发展，为 OSCC 提供了一种潜在的治疗方法。
