Department of Otolaryngology, First Affiliated Hospital of China Medical University, Shenyang, China.
Eur Rev Med Pharmacol Sci. 2020 Apr;24(8):4314-4319. doi: 10.26355/eurrev_202004_21012.
This study aims to investigate whether inflammatory response or oxidative stress could induce upregulation of PTPN2, thus promoting the progression of laryngocarcinoma.
PTPN2 levels in laryngocarcinoma tissues and normal tissues were detected. In addition, PTPN2 levels in laryngocarcinoma tissues with stage 1/2 or stage 3/4 were determined as well. In vitro abundance of PTPN2 was measured in laryngocarcinoma cells and immortalized human nasopharyngeal epithelial cells. Survival analysis was conducted in laryngocarcinoma patients with high or low expression level of PTPN2. Subsequently, M4E cells were stimulated with inflammation (IFN-γ or TNF-α treatment) or oxidative stress (H2O2 stimulation), followed by determination of the protein level of PTPN2. In M4E cells stimulated with different concentrations of H2O2, the clonality and Ki-67 positive cell ratio were detected. Finally, clonality and Ki-67 positive cell ratio in M4E cells transfected with negative control or sh-PTPN2, regardless of H2O2 stimulation, were assessed.
PTPN2 was upregulated in laryngocarcinoma tissues, especially those in stage 3/4. Similarly, in vitro abundance of PTPN2 was higher in laryngocarcinoma cell lines. The high level of PTPN2 predicted poor prognosis in laryngocarcinoma patients. IFN-γ or TNF-α treatment upregulated the protein level of PTPN2. Meanwhile, H2O2 stimulation upregulated the protein level of PTPN2, dose-dependently increased clonality, and Ki-67 positive cell ratio in M4E cells. The knockdown of PTPN2 suppressed clonality and Ki-67 positive cell ratio in M4E cells stimulated by H2O2 or not.
Inflammatory response or oxidative stress could induce upregulation of PTPN2, thus promoting the proliferative ability of laryngocarcinoma.
本研究旨在探讨炎症反应或氧化应激是否会诱导 PTPN2 的上调，从而促进喉癌的进展。
检测了喉癌组织和正常组织中的 PTPN2 水平。此外，还测定了分期为 1/2 期或 3/4 期的喉癌组织中的 PTPN2 水平。在喉癌细胞和永生化人鼻咽上皮细胞中测量 PTPN2 的体外丰度。对 PTPN2 高表达或低表达的喉癌患者进行生存分析。随后，用炎症（IFN-γ或 TNF-α处理）或氧化应激（H2O2 刺激）刺激 M4E 细胞，然后测定 PTPN2 的蛋白水平。在用不同浓度 H2O2 刺激的 M4E 细胞中，检测克隆形成和 Ki-67 阳性细胞比例。最后，无论是否用 H2O2 刺激，检测转染阴性对照或 sh-PTPN2 的 M4E 细胞的克隆形成和 Ki-67 阳性细胞比例。
PTPN2 在喉癌组织中上调，尤其是在分期为 3/4 期的组织中上调。同样，在体外，喉癌细胞系中 PTPN2 的丰度也较高。PTPN2 高水平预示着喉癌患者预后不良。IFN-γ或 TNF-α处理上调了 PTPN2 的蛋白水平。同时，H2O2 刺激呈剂量依赖性地上调了 M4E 细胞中 PTPN2 的蛋白水平，增加了克隆形成和 Ki-67 阳性细胞比例。在 H2O2 刺激或不刺激的情况下，敲低 PTPN2 抑制了 M4E 细胞的克隆形成和 Ki-67 阳性细胞比例。
炎症反应或氧化应激可诱导 PTPN2 的上调，从而促进喉癌的增殖能力。
