Department of Stomatology, Jining No. 1 People's Hospital, Jining, Shandong, China.
Eur Rev Med Pharmacol Sci. 2020 Jun;24(12):6716-6725. doi: 10.26355/eurrev_202006_21659.
We explored the IgG1 heavy chain constant region (IGHG1) roles in tongue squamous cell carcinoma (TSCC) progression, as well as to probe the underlying mechanisms.
The expression patterns of IGHG1 in TSCC tissues and cell lines were tested by Western blotting, quantitative real-time PCR (RT-PCR) and immunohistochemistry (IHC) technologies. The relationship between IGHG1 expression level and the overall survival and clinicopathologic features of patients with TSCC were evaluated to assess the clinical value of IGHG1. The effects of IGHG1 on cell function were determined by Cell-Counting Kit-8 (CCK-8), clone formation, flow cytometry and in vivo tumor formation assays.
The expression of IGHG1 in TSCC tissues and cell lines was significantly elevated at both mRNA and protein levels. IGHG1 expression levels closely related to T classification (p=0.008), clinical stage (p=0.011), and node metastasis (p=0.005) in TSCC patients. Upregulation of IGHG1 with lentivirus infection significantly increased Janus kinase 1 (JAK1) expression and the phosphorylation level of signal transducer and activator of transcription 5 (STAT5). In addition, IGHG1 overexpression markedly enhanced cell proliferation, clone formation and tumorigenesis and inhibited cell apoptosis, whereas these effects were abolished when JAK1 was downregulated in SCC15 and SCC4 TSCC cell lines.
Collectively, this study reveals that IGHG1 functions as an oncogene in TSCC via activating JAK1/STAT5 signaling.
我们探索了 IgG1 重链恒定区（IGHG1）在舌鳞状细胞癌（TSCC）进展中的作用，并探讨了其潜在机制。
通过 Western blot、定量实时 PCR（RT-PCR）和免疫组织化学（IHC）技术检测 IGHG1 在 TSCC 组织和细胞系中的表达模式。评估 IGHG1 表达水平与 TSCC 患者总生存率和临床病理特征的关系，以评估 IGHG1 的临床价值。通过细胞计数试剂盒-8（CCK-8）、克隆形成、流式细胞术和体内肿瘤形成实验确定 IGHG1 对细胞功能的影响。
IGHG1 在 TSCC 组织和细胞系中的表达在 mRNA 和蛋白水平上均显著升高。IGHG1 的表达水平与 TSCC 患者的 T 分类（p=0.008）、临床分期（p=0.011）和淋巴结转移（p=0.005）密切相关。慢病毒感染上调 IGHG1 显著增加了 Janus 激酶 1（JAK1）的表达和信号转导和转录激活因子 5（STAT5）的磷酸化水平。此外，IGHG1 过表达显著增强了 SCC15 和 SCC4 TSCC 细胞系中的细胞增殖、克隆形成和肿瘤发生，抑制了细胞凋亡，而当 JAK1 在 SCC15 和 SCC4 TSCC 细胞系中被下调时，这些效应被消除。
综上所述，本研究表明 IGHG1 通过激活 JAK1/STAT5 信号通路在 TSCC 中发挥癌基因作用。
