Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, China.
Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Cell Biochem. 2019 Nov;120(11):19044-19051. doi: 10.1002/jcb.29227. Epub 2019 Jun 26.
Malignant glioma remains the most frequent form of primary brain tumors all over the world. The gliomagenesis is characterized by various molecular processes such as neoplastic transformation, dysregulation of the cell cycle, and angiogenesis. Among these biomolecular events, the existence of inflammation and oxidative stress pathways in the development of glioma has been reported. PTPN2 is associated with several inflammatory disorders. However, the biological role of PTPN2 in inflammation responses and oxidative stress pathways involved in glioma remains poorly known. Here, we focused on its function in glioma development. Here, we observed that PTPN2 was significantly increased in glioma especially in a grade-dependent manner. Meanwhile, interferon-γ and tumor necrosis factor-α, which have been identified as crucial inflammation cytokines, were able to trigger PTPN2 expression in a dose-dependent course in T98G cells. Then, we found that PTPN2 was oxidated and inactivated by H O . Meanwhile, H O induced glioma cell colony formation capacity and increased ki-67 expression confirmed by flow cytometry assay. Finally, T98G cells were transfected with PTPN2 shRNA and it was shown that knockdown of PTPN2 obviously inhibited T98G cell colony formation and induced cell apoptosis. In summary, our findings indicated that PTPN2 could be induced by inflammatory response and oxidative stress and its deficiency depressed glioma cell growth.
恶性脑胶质瘤仍然是全世界最常见的原发性脑肿瘤。神经胶质瘤的发生特征是多种分子过程，如肿瘤转化、细胞周期失调和血管生成。在这些生物分子事件中，已有报道称炎症和氧化应激途径存在于胶质瘤的发展中。PTPN2 与几种炎症性疾病有关。然而，PTPN2 在炎症反应和涉及胶质瘤的氧化应激途径中的生物学作用仍知之甚少。在这里，我们专注于它在胶质瘤发展中的功能。在这里，我们观察到 PTPN2 在神经胶质瘤中特别是在分级依赖的方式中显著增加。同时，干扰素-γ和肿瘤坏死因子-α，它们已被鉴定为关键的炎症细胞因子，能够在 T98G 细胞中以剂量依赖的方式触发 PTPN2 的表达。然后，我们发现 PTPN2 被 H O 氧化和失活。同时，H O 诱导的胶质瘤细胞集落形成能力和增加的 ki-67 表达通过流式细胞术检测得到证实。最后，T98G 细胞用 PTPN2 shRNA 转染，结果表明 PTPN2 的敲低明显抑制了 T98G 细胞集落形成并诱导细胞凋亡。总之，我们的研究结果表明，PTPN2 可以被炎症反应和氧化应激诱导，其缺乏会抑制神经胶质瘤细胞的生长。
