{"title":"MerTK is Ectopically Expressed and Affects the Biological Function in Diffuse Large B-Cell Lymphoma","authors":"Yan Li, Cunzhen Shi, Jiazhuo Wu, Xiaoyan Feng, Wenting Song, Mengyuan Jin, Yu Chang, Lijuan Han, Ping Zhang, Yuqin Song, Jun Zhu, Mingzhi Zhang","doi":"10.1002/hon.70089","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Relapsed/refractory diffuse large B-cell lymphoma (DLBCL) patients do not receive standard rescue treatment; therefore, the exploration of new therapeutic targets for the treatment of DLBCL is urgently needed. Immunohistochemistry and western blotting were performed to determine the expression of MerTK in DLBCL. Targeted knockdown of MerTK by shRNA was conducted in DLBCL cell lines. DLBCL cell-derived xenograft models were established to evaluate the effects of MerTK in vivo. We found for the first time that MerTK, a proto-oncogene, is aberrantly highly expressed in DLBCL samples and cell lines. Targeted knockdown of MerTK or application of UNC2025, a small inhibitor of MerTK, can inhibit DLBCL cell proliferation, promote apoptosis, and inhibit G2/M phase arrest. Transcriptome sequencing was performed after targeted knockdown of MerTK, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the differentially expressed genes involved in the autophagy pathway, in which the expression of ANXA1 was significantly upregulated, were significantly enriched. Further studies revealed that targeted MerTK knockdown inhibited autophagy flow by increasing the expression of ANXA1 in DLBCL cells. Overexpression of ANXA1 decreased proliferation and autophagy flow in DLBCL cells. Targeted knockdown of MerTK decreased disease progression in a mouse xenograft DLBCL model in vivo. UNC2025 inhibited tumor growth in a DLBCL cell-derived xenograft model. Therefore, MerTK is ectopically expressed in DLBCL, and targeted inhibition of MerTK suppresses the growth of DLBCL in vitro and in vivo. This study provides clues for precision therapy for DLBCLs that target MerTK.</p>\n </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 3","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hematological Oncology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/hon.70089","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Relapsed/refractory diffuse large B-cell lymphoma (DLBCL) patients do not receive standard rescue treatment; therefore, the exploration of new therapeutic targets for the treatment of DLBCL is urgently needed. Immunohistochemistry and western blotting were performed to determine the expression of MerTK in DLBCL. Targeted knockdown of MerTK by shRNA was conducted in DLBCL cell lines. DLBCL cell-derived xenograft models were established to evaluate the effects of MerTK in vivo. We found for the first time that MerTK, a proto-oncogene, is aberrantly highly expressed in DLBCL samples and cell lines. Targeted knockdown of MerTK or application of UNC2025, a small inhibitor of MerTK, can inhibit DLBCL cell proliferation, promote apoptosis, and inhibit G2/M phase arrest. Transcriptome sequencing was performed after targeted knockdown of MerTK, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the differentially expressed genes involved in the autophagy pathway, in which the expression of ANXA1 was significantly upregulated, were significantly enriched. Further studies revealed that targeted MerTK knockdown inhibited autophagy flow by increasing the expression of ANXA1 in DLBCL cells. Overexpression of ANXA1 decreased proliferation and autophagy flow in DLBCL cells. Targeted knockdown of MerTK decreased disease progression in a mouse xenograft DLBCL model in vivo. UNC2025 inhibited tumor growth in a DLBCL cell-derived xenograft model. Therefore, MerTK is ectopically expressed in DLBCL, and targeted inhibition of MerTK suppresses the growth of DLBCL in vitro and in vivo. This study provides clues for precision therapy for DLBCLs that target MerTK.
期刊介绍：
Hematological Oncology considers for publication articles dealing with experimental and clinical aspects of neoplastic diseases of the hemopoietic and lymphoid systems and relevant related matters. Translational studies applying basic science to clinical issues are particularly welcomed. Manuscripts dealing with the following areas are encouraged:
-Clinical practice and management of hematological neoplasia, including: acute and chronic leukemias, malignant lymphomas, myeloproliferative disorders
-Diagnostic investigations, including imaging and laboratory assays
-Epidemiology, pathology and pathobiology of hematological neoplasia of hematological diseases
-Therapeutic issues including Phase 1, 2 or 3 trials as well as allogeneic and autologous stem cell transplantation studies
-Aspects of the cell biology, molecular biology, molecular genetics and cytogenetics of normal or diseased hematopoeisis and lymphopoiesis, including stem cells and cytokines and other regulatory systems.
Concise, topical review material is welcomed, especially if it makes new concepts and ideas accessible to a wider community. Proposals for review material may be discussed with the Editor-in-Chief. Collections of case material and case reports will be considered only if they have broader scientific or clinical relevance.
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