非霍奇金氏淋巴瘤已成为威胁人类健康的恶性肿瘤之一，需要寻找新的治疗药物及方法有效地治疗复发难治性患者并延长其生存期。靶向具有起始、维持肿瘤能力的干细胞已经成为淋巴瘤治疗的首要目标，而降低关键原癌蛋白的表达是抑制淋巴瘤干细胞的新策略。假性激酶TRIB3是一种压力和代谢应激蛋白，与肿瘤发生发展密切相关。我们最近发现，非霍奇金氏淋巴瘤组织高表达TRIB3，敲除TRIB3抑制淋巴瘤生长和肿瘤干性，并显著降低C-Myc等多个促肿瘤因子表达。但TRIB3如何调节促肿瘤因子表达、促进淋巴瘤发生发展的机制尚不明确。为此，我们将采用体内外模型，从临床-动物-细胞-分子四个层次，确定TRIB3是否通过与C-Myc等促肿瘤因子发生相互作用参与淋巴瘤干性维持，进而发挥促淋巴瘤效应；阐明TRIB3调节C-Myc等促肿瘤因子表达的分子机制。本研究不但揭示TRIB3促淋巴瘤的生物学机制，也为抗淋巴瘤药物研发提供新思路。

Patients with relapsed/refractory Non-Hodgkin's lymphoma (NHL) have a dismal prognosis, which makes NHL become one of the most serious types of malignant tumors. Currently there is an urgent need for novel agents and new treatment options for NHL therapy. Targeting lymphoma stem cells inhibits tumorigenesis, drug resistance and recurrence through the reduction of key oncoprotein expressions, which is considered as a new strategy of NHL treatment. Pseudokinase TRIB3 acts as a metabolic stress protein, which is closely related to the tumour occurrence and development. We recently found that TRIB3 was highly expressed in non-Hodgkin's lymphoma tissues, and TRIB3 depletion inhibited lymphoma growth and stem-like traits, and reduced the expressions of multiple tumor-promoting factors including C-Myc and Ras. Based on our previous findings, we intend to use in vitro cell models, transgenic animal models, PDX models and clinical specimens to investigate the molecular mechanism of TRIB3 in the lymphoma development and progression by interacting with the key tumor-promoting factors. This study may not only provide new insights into the specific mechanism of TRIB3 in the pathogenesis of NHL, but also provide clues and opportunity for the development of anti-lymphoma drugs.