Department of Medical Oncology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.
Department of Hematology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region, China.
Bioengineered. 2022 Mar;13(3):7607-7621. doi: 10.1080/21655979.2022.2048772.
About 40% of patients with diffuse large B-cell lymphoma (DLBCL) develop drug resistance after first-line chemotherapy, which remains a major cause of morbidity and mortality. The emergence of DLBCL drug resistance is mainly related to Adriamycin. Our previous research shows that Paclitaxel could be a potential therapeutic drug for the treatment of Adriamycin-resistant DLBCL. Based on the results of RNA-seq and integrated network analysis, we study the potential molecular mechanism of Paclitaxel in the treatment of Adriamycin-resistant DLBCL in multiple dimensions. A CCK-8 assay showed that the inhibitory effect of Paclitaxel on Pfeiffer and Pfeiffer/ADM (Adriamycin-resistant DLBCL cell lines) is significantly higher than that of Adriamycin ( ＜ 0.05). Five hub genes (UBC, TSR1, WDR46, HSP90AA1, and NOP56) were obtained via network analysis from 971 differentially expressed genes (DEGs) based on the RNA-seq of Paclitaxel-intervened Pfeiffer/ADM. The results of the network function module analysis showed that the inhibition of Pfeiffer/ADM by Paclitaxel was closely related to ribosome biosynthesis in eukaryotes. The results of RT-qPCR showed that the mRNA levels of the five hub genes in the Pfeiffer/ADM group were significantly lower than those in the Pfeiffer group and the Pfeiffer/ADM Paclitaxel-treated group ( ＜ 0.05). Consistent with studies, Paclitaxel exhibited a significant inhibitory effect on Adriamycin-resistant DLBCL, which may have played a role in the five hub genes (UBC, TSR1, WDR46, HSP90AA1 and NOP56) and ribosome biosynthesis in eukaryotes pathway, but the specific regulation needs further experimental verification.
约 40%的弥漫性大 B 细胞淋巴瘤（DLBCL）患者在一线化疗后产生耐药性，这仍然是发病率和死亡率的主要原因。DLBCL 耐药性的出现主要与阿霉素有关。我们之前的研究表明，紫杉醇可能是治疗阿霉素耐药性 DLBCL 的潜在治疗药物。基于 RNA-seq 和综合网络分析的结果，我们从多个维度研究紫杉醇治疗阿霉素耐药性 DLBCL 的潜在分子机制。CCK-8 检测结果表明，紫杉醇对 Pfeiffer 和 Pfeiffer/ADM（阿霉素耐药性 DLBCL 细胞系）的抑制作用明显高于阿霉素（＜0.05）。通过基于 RNA-seq 的 Paclitaxel 干预 Pfeiffer/ADM 的 971 个差异表达基因（DEGs）的网络分析，获得了 5 个枢纽基因（UBC、TSR1、WDR46、HSP90AA1 和 NOP56）。网络功能模块分析结果表明，紫杉醇对 Pfeiffer/ADM 的抑制作用与真核生物核糖体生物合成密切相关。RT-qPCR 结果显示，Pfeiffer/ADM 组中 5 个枢纽基因的 mRNA 水平明显低于 Pfeiffer 组和 Paclitaxel 处理后的 Pfeiffer/ADM 组（＜0.05）。与研究一致，紫杉醇对阿霉素耐药性 DLBCL 表现出显著的抑制作用，可能与 5 个枢纽基因（UBC、TSR1、WDR46、HSP90AA1 和 NOP56）和真核生物核糖体生物合成途径有关，但具体的调控需要进一步的实验验证。
