Sun Kan-Da, Ni Yi-Jiang, Qin Hui, Xu Qing-Feng
Department of Stomatology, The Second Affiliated Hospital of Changzhou, Nanjing Medical University, Changzhou, China.
Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Changzhou, Nanjing Medical University, Changzhou, China.
Kaohsiung J Med Sci. 2022 Oct;38(10):950-959. doi: 10.1002/kjm2.12572. Epub 2022 Aug 30.
Oral squamous cell carcinoma (OSCC) is one of the most frequent malignancies found in head and neck cancers. Dysregulation of lncRNAs has been proposed to be related to the development of OSCC. Here, we investigated the function and probable mechanisms of lncRNA DLEU1 in OSCC. OSCC cell lines and human oral keratinocytes (HOKs) were cultured, while SCC-25 and CAL-27 cells were transfected with the corresponding plasmids. Reverse transcription quantitative PCR (RT-qPCR) and western blot were carried out to measure the RNA and protein levels. Cell proliferation, migration and invasion were evaluated using MTT assays, wound healing and Transwell assays. The StarBase database predicted the interactions between DLEU1 and miR-126-5p, as well as miR-126-5p and GAB1, which were further validated using a dual-luciferase reporter assay. Our results indicated that DLEU1 and GAB1 were upregulated, while miR-126-5p was downregulated in OSCC cells. Silencing DLEU1 reduced OSCC cell proliferation, migration, and invasion, while DLEU1 overexpression had the opposite effects. DLEU1 mediated biological effects in OSCC through binding to miR-126-5p, which directly targeted GAB1. miR-126-5p knockdown rescued the inhibitory function of DLEU1 depletion on proliferation, migration and invasion. Meanwhile, the miR-126-5p mimic exerted suppressive functions in the progression of OSCC, which were neutralized after GAB1 overexpression. In summary, lncRNA DLEU1 targets the miR-126-5p/GAB1 axis to aggravate OSCC progression, providing a novel target for treating OSCC.
口腔鳞状细胞癌（OSCC）是头颈部癌症中最常见的恶性肿瘤之一。lncRNAs的失调被认为与OSCC的发生发展有关。在此，我们研究了lncRNA DLEU1在OSCC中的功能及可能机制。培养OSCC细胞系和人口腔角质形成细胞（HOKs），并将相应质粒转染至SCC - 25和CAL - 27细胞。采用逆转录定量PCR（RT - qPCR）和蛋白质印迹法检测RNA和蛋白质水平。通过MTT实验、伤口愈合实验和Transwell实验评估细胞增殖、迁移和侵袭能力。StarBase数据库预测了DLEU1与miR - 126 - 5p以及miR - 126 - 5p与GAB1之间的相互作用，并通过双荧光素酶报告基因实验进一步验证。我们的结果表明，在OSCC细胞中DLEU1和GAB1上调，而miR - 126 - 5p下调。沉默DLEU1可降低OSCC细胞的增殖、迁移和侵袭能力，而DLEU1过表达则产生相反的效果。DLEU1通过与miR - 126 - 5p结合介导OSCC中的生物学效应，miR - 126 - 5p直接靶向GAB1。敲低miR - 126 - 5p可挽救DLEU1缺失对增殖、迁移和侵袭的抑制作用。同时，miR - 126 - 5p模拟物在OSCC进展中发挥抑制作用，在GAB1过表达后被中和。总之，lncRNA DLEU1靶向miR - 126 - 5p/GAB1轴以加重OSCC进展，为治疗OSCC提供了新靶点。
