Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
Aging (Albany NY). 2020 Nov 16;12(24):25020-25034. doi: 10.18632/aging.103969.
The pseudokinase Tribble 3 (TRIB3) is known as a regulator in cellular responses to a variety of stresses, such as glucose insufficiency and endoplasmic reticulum (ER) stress. TRIB3 is upregulated in various cancer tissues and is closely connected to the poor prognosis of patients. However, the underlying regulation and function of TRIB3 in glioblastoma (GBM) is still largely unknown. In this study, the upregulation of TRIB3 was confirmed both in primary specimens from GBM patients and with GBM cell lines. Overexpression of specific TRIB3 transcripts promoted cell growth and migration , while knockdown of TRIB3 expression exerted a repressive effect on these cellular processes. The growth-promoting effect of TRIB3 was also demonstrated in a xenograft mouse model. Mechanistic studies further revealed that TRIB3 was able to suppress autophagic flux and that this suppression was responsible for TRIB3 silencing-induced proliferation and migration of GBM cells. These findings indicate that the suppression of autophagic flux by TRIB3 drives the invasion and proliferation of GBM cells, thus suggesting that TRIB3 is a potential novel therapeutic target for the treatment of glioma.
假激酶 Tribble 3（TRIB3）作为细胞对各种应激（如葡萄糖不足和内质网应激）反应的调节剂而闻名。TRIB3 在各种癌症组织中上调，与患者的不良预后密切相关。然而，TRIB3 在胶质母细胞瘤（GBM）中的潜在调节和功能仍在很大程度上未知。在这项研究中，在 GBM 患者的原发性标本和 GBM 细胞系中均证实了 TRIB3 的上调。特定 TRIB3 转录本的过表达促进了细胞生长和迁移，而 TRIB3 表达的敲低对这些细胞过程产生了抑制作用。TRIB3 在异种移植小鼠模型中也表现出了促生长作用。机制研究进一步表明，TRIB3 能够抑制自噬通量，并且这种抑制是 TRIB3 沉默诱导的 GBM 细胞增殖和迁移的原因。这些发现表明，TRIB3 通过抑制自噬通量来驱动 GBM 细胞的侵袭和增殖，因此提示 TRIB3 可能是治疗神经胶质瘤的一个潜在的新型治疗靶点。
