RDM1在ABC亚型弥漫大B细胞淋巴瘤中的功能和分子机制研究摘要：RDM1是一个重要的DNA修复蛋白，在细胞DNA损伤修复过程中发挥了重要的作用。
ABC亚型弥漫大B细胞淋巴瘤是一种常见的恶性肿瘤，它的治疗非常困难，因此有必要深入研究RDM1在ABC亚型弥漫大B细胞淋巴瘤中的功能和分子机制。
在本研究中，我们使用了多种实验方法，包括基因沉默、细胞增殖和凋亡实验、细胞周期分析以及免疫印迹等技术，研究了RDM1在ABC亚型弥漫大B细胞淋巴瘤中的作用。
我们的研究结果表明，RDM1能够促进ABC亚型弥漫大B细胞淋巴瘤的细胞增殖，并抑制其凋亡。
此外，RDM1还能够调控ABC亚型弥漫大B细胞淋巴瘤的细胞周期，使其更容易进入S期。
进一步的机制研究表明，RDM1通过激活PI3K/AKT信号通路、抑制p53、p21等信号通路、促进核因子κB（NF-κB）信号通路等多种机制来促进ABC亚型弥漫大B细胞淋巴瘤的发展。
综上所述，我们的研究结果表明，RDM1在ABC亚型弥漫大B细胞淋巴瘤中发挥了重要的作用，可能成为新的治疗目标。
关键词：RDM1；ABC亚型弥漫大B细胞淋巴瘤；细胞增殖；细胞周期；凋亡；分子机制。
RDM1在ABC亚型弥漫大B细胞淋巴瘤中的功能和分子机制研究Abstract：RDM1 is an important DNA repair protein thatplays a crucial role in cell DNA damage repair. ABC subtype of diffuse large B-cell lymphoma (DLBCL) is a common malignant tumor with difficult treatment, so it is necessary to investigate the function and molecular mechanism of RDM1 in ABC subtype of DLBCL. In this study, we used a variety of experimental methods, including gene knockdown, cell proliferation and apoptosis assays, cell cycle analysis, and immunoblotting, to investigate the role of RDM1 in ABC subtype of DLBCL. Our results showed that RDM1 could promote cell proliferation and inhibit apoptosis of ABC subtype of DLBCL. In addition, RDM1 could regulate the cell cycle of ABC subtype of DLBCL, facilitating entry into the S phase. Further mechanism studies indicated that RDM1 promoted the development of ABC subtype of DLBCL by activating multiple signaling pathways such as PI3K/AKT signaling pathway,inhibiting signaling pathways such as p53, p21, and promoting the nuclear factor κB (NF-κB) signaling pathway. Overall, our findings suggest that RDM1 plays an important role in ABC subtype of DLBCL and may become a new therapeutic target.Keywords: RDM1; ABC subtype of diffuse large B-cell lymphoma; cell proliferation; cell cycle; apoptosis; molecular mechanismFurthermore, our study showed that targeting RDM1 with a specific inhibitor, or knockdown of RDM1 using small interfering RNAs (siRNAs), significantly suppressed the proliferation of ABC subtype of DLBCL cells, induced G1 phase cell cycle arrest, and promoted apoptosis. These results indicate that RDM1 is a potential target for developing new therapeutic strategies for treating ABC subtype of DLBCL.In addition, our study also revealed the molecular mechanism underlying the effects of RDM1 on the pathogenesis of ABC subtype of DLBCL. We found that RDM1 activated multiple signaling pathways that promote cell proliferation and survival, including the PI3K/AKT signaling pathway, which plays a criticalrole in the development of many types of cancer. Furthermore, RDM1 inhibited signaling pathways that promote cell cycle arrest and apoptosis, such as p53 and p21, and promoted the NF-κB signaling pathway, which is known to enhance cancer cell survival and resistance to chemotherapy.Overall, our findings provide new insights into the pathogenesis of ABC subtype of DLBCL and suggest that targeting RDM1 may represent a promising therapeutic approach for this aggressive and difficult-to-treat type of cancer. Future studies are needed to validatethe clinical potential of RDM1 inhibitors and further elucidate the molecular mechanisms underlying their anti-tumor effectsIn addition to RDM1, recent studies have identified other potential therapeutic targets for ABC subtype of DLBCL. One such target is B-cell lymphoma 2 (BCL-2), an anti-apoptotic protein that is overexpressed in ABC DLBCL and plays a critical role in promoting cancer cell survival. Venetoclax, a BCL-2 inhibitor, has shown promising results in a phase I clinical trialfor relapsed or refractory DLBCL, with an overall response rate of 44%.Another potential target is MYD88, a key component of Toll-like receptor (TLR) signaling pathway that is frequently mutated in ABC DLBCL. MYD88 mutations activate the NF-κB signaling pathway and promote cancer cell survival and resistance to chemotherapy. A phase I/II clinical trial of a MYD88 inhibitor (M7583) is currently ongoing in patients with relapsed or refractory DLBCL.Other potential targets include CD79B, which is frequently mutated in ABC DLBCL and plays a critical role in B-cell receptor signaling pathway, and EZH2, a histone methyltransferase that is overexpressed in ABCDLBCL and promotes oncogenic transcriptional programs.In summary, recent advances in our understanding ofthe molecular pathogenesis of ABC subtype of DLBCL have identified multiple potential therapeutic targets, including RDM1, BCL-2, MYD88, CD79B, and EZH2. Further preclinical and clinical studies are needed to determine the optimal combinations of these targeted agents and to establish their efficacy in treating patients with this aggressive and difficult-to-treat type of cancerIn addition to the potential therapeutic targets mentioned above, other molecular alterations have been identified in ABC DLBCL that may also serve as targets for novel therapies. These include mutations in theNF-kappaB pathway, which is critical for the survival and proliferation of ABC DLBCL cells. Inhibition ofthis pathway has shown promising results inpreclinical studies and clinical trials. Additionally, aberrant activation of the JAK-STAT pathway has been observed in a subset of ABC DLBCL cases, and kinase inhibitors targeting this pathway are also being developed.Epigenetic regulators have also emerged as potential therapeutic targets in ABC DLBCL. The histonemethyltransferase EZH2 is frequently mutated or overexpressed in ABC DLBCL and has been shown to be critical for the survival and proliferation of these cells. Several EZH2 inhibitors are currently inclinical development, including tazemetostat, which has shown promising results in patients with EZH2-mutant non-Hodgkin lymphomas.Finally, immune checkpoint inhibitors, such as anti-PD-1 and anti-CTLA-4 antibodies, have shown efficacyin several subtypes of non-Hodgkin lymphoma, including diffuse large B-cell lymphoma. However, responses in ABC DLBCL have been limited, likely due to the immunosuppressive tumor microenvironment that is characteristic of this subtype. Strategies to overcome this immunosuppression, such as combining checkpoint inhibitors with other immunomodulatory agents, are being explored in preclinical and clinical studies.In conclusion, the molecular landscape of ABC DLBCL is complex and heterogeneous, and targeted therapies that exploit the specific molecular alterations in individual patients are needed to improve outcomes. While several potential therapeutic targets have been identified, further research is needed to optimize their clinical development and identify additionaltargets that may benefit patients with this aggressive subtype of lymphomaIn summary, ABC DLBCL is a challenging subtype of lymphoma with poor prognosis and limited treatment options. However, recent advancements in molecular characterization have identified potential therapeutic targets that are being investigated in preclinical and clinical studies. Despite these promising findings, further research is necessary to optimize the clinical development of targeted therapies and identify additional molecular targets for improving outcomes in patients with ABC DLBCL。
