Wang Yan, Li Banban, Zhao Yanan, Zhu Xunxun, Wang Bo, Yang Lizhe, Feng Rui, Teng Qingliang
Department of Hematology, The Affiliated Taian City Central Hospital of Qingdao University, Taian, China.
Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Hematol Oncol. 2025 Jul;43(4):e70119. doi: 10.1002/hon.70119.
Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Tripartite motif containing 44 (TRIM44) belonging to the TRIM family, is involved in tumor development and is highly expressed in a variety of tumors. However, the role of TRIM44 in DLBCL remains undefined. Gain and loss-of-function studies were performed on lymphoblast cell lines DB and SU-DHL-4 to investigate its function. TRIM44 overexpression significantly promoted cell proliferation and viability, whereas its silencing inhibited proliferation and induced apoptosis. TRIM44 overexpression upregulated the LC3II/LC3-I ratio and Beclin1 expression, as well as increased autophagosomes formation, suggesting autophagy activation. Notably, TRIM44 conferred chemoresistance to doxorubicin in DB cells by increasing autophagic activity. In vivo study on mice revealed that TRIM44 overexpression increased Ki67 and PCNA expression, suggesting an increased tumor growth. Our previous work revealed that miR-665 is a tumor suppressor in DLBCL. The results of miRNA pull-down and luciferase reporter assay indicated that TRIM44 was a direct target of miR-665. In conclusion, TRIM44 promoted DLBCL progression by increasing autophagy-mediated chemoresistance, revealing the involvement of miR-665/TRIM44 axis.
弥漫性大B细胞淋巴瘤（DLBCL）是非霍奇金淋巴瘤最常见的亚型。含三联基序蛋白44（TRIM44）属于TRIM家族，参与肿瘤发生发展，在多种肿瘤中高表达。然而，TRIM44在DLBCL中的作用尚不清楚。我们对淋巴母细胞系DB和SU-DHL-4进行了功能获得和功能缺失研究，以探究其功能。TRIM44过表达显著促进细胞增殖和活力，而其沉默则抑制增殖并诱导凋亡。TRIM44过表达上调了LC3II/LC3-I比值和Beclin1表达，同时增加了自噬体形成，提示自噬激活。值得注意的是，TRIM44通过增加自噬活性使DB细胞对阿霉素产生耐药性。对小鼠的体内研究表明，TRIM44过表达增加了Ki67和PCNA表达，提示肿瘤生长加快。我们之前的研究表明，miR-665是DLBCL中的一种肿瘤抑制因子。miRNA下拉实验和荧光素酶报告基因检测结果表明，TRIM44是miR-665的直接靶点。总之，TRIM44通过增加自噬介导的化疗耐药性促进DLBCL进展，揭示了miR-665/TRIM44轴的作用。
