Nioka Kohei, Ichimura Norihisa, Ikutomi Shohei, Hibi Hideharu
Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Oral and Maxillofacial Surgery, Nagoya University Hospital, Nagoya, Japan.
Nagoya J Med Sci. 2025 May;87(2):211-219. doi: 10.18999/nagjms.87.2.211.
Taurine upregulated 1 (TUG1), whose function is associated with tumor development, is a relatively new long non-coding RNA. TUG1 is overexpressed in multiple types of cancers. However, in head and neck squamous cell carcinoma (HNSCC), the behavior of TUG1 has not yet been completely elucidated. Therefore, we aimed to clarify the function of TUG1 in HNSCC and develop a novel therapeutic target. We analyzed the expression levels of TUG1 in patients with HNSCC using The Cancer Genome Atlas dataset and human oral keratinocytes, and five HNSCC cell lines (HSC-4, Sa3, HSQ-89, SAS, and Ca9-22) through quantitative reverse-transcription polymerase chain reaction. The biological role of TUG1 in HNSCC was investigated using cell growth and migration assays with antisense oligonucleotides in Ca9-22 and SAS cell lines. TUG1 target genes were identified via microarray analysis. The TUG1 expression level was considerably higher in tumor than in normal tissues, and the same result was observed in human oral keratinocytes and all HNSCC cell lines. TUG1 knockdown dramatically inhibited cell proliferation and migration. Furthermore, we identified nemo-like kinase, which may change in tandem with TUG1 expression. Our findings indicate the possibility for targeting the TUG1-nemo-like kinase axis as a novel approach for the treatment of HNSCC.
牛磺酸上调基因1(TUG1)是一种相对较新的长链非编码RNA,其功能与肿瘤发展相关。TUG1在多种癌症中均有过表达。然而,在头颈部鳞状细胞癌(HNSCC)中,TUG1的表现尚未完全阐明。因此,我们旨在阐明TUG1在HNSCC中的功能,并开发一种新的治疗靶点。我们通过定量逆转录聚合酶链反应,利用癌症基因组图谱数据集、人类口腔角质形成细胞以及五种HNSCC细胞系(HSC-4、Sa3、HSQ-89、SAS和Ca9-22)分析了HNSCC患者中TUG1的表达水平。我们使用反义寡核苷酸在Ca9-22和SAS细胞系中进行细胞生长和迁移试验,研究了TUG1在HNSCC中的生物学作用。通过微阵列分析鉴定了TUG1的靶基因。TUG1在肿瘤组织中的表达水平显著高于正常组织,在人类口腔角质形成细胞和所有HNSCC细胞系中也观察到了相同的结果。TUG1基因敲低显著抑制了细胞增殖和迁移。此外,我们鉴定出了类Nemo样激酶,其可能与TUG1表达协同变化。我们的研究结果表明,靶向TUG1-类Nemo样激酶轴可能是一种治疗HNSCC的新方法。