CRIP1 involves the pathogenesis of multiple myeloma via dual-regulation of proteasome and autophagy

Multiple myeloma (MM) is an incurable hematological malignancy of plasma cells. The maintenance of protein homeostasis is critical for the survival of MM cells. The excess paraprotein in MM cells undergoes clearance through proteasomes or lysosomes, two inter-connected yet independent pathways. While proteasome inhibitors (PIs) serve as fundamental agents significantly improving patient outcomes, heightened autophagy activity diminishes sensitivity to PI treatment.Elevated CRIP1 levels serve as a biomarker for relapsed/refractory MM and correlate with shorter overall patient survival. To further comprehend the role of CRIP1 in multiple myeloma pathogenesis, we conducted transcriptome sequencing. Overall design: To investigate the role of CRIP1 in multiple myeloma pathogenesis, we generated multiple myeloma cells with CRIP1 knockdown by transfecting them with CRIP1-shRNA, utilizing Scramble-shRNA as a control. RNA sequencing was performed on both KMS11-CRIP1-sh and KMS11-Scr (control) cell lines, each replicated three times for biological validation.

多发性骨髓瘤（Multiple myeloma, MM）是一类不可治愈的浆细胞源性血液系统恶性肿瘤。蛋白质稳态的维持对于骨髓瘤细胞的存活至关重要。骨髓瘤细胞内过量的副蛋白可通过蛋白酶体与溶酶体这两条相互关联却彼此独立的通路完成清除。尽管蛋白酶体抑制剂（proteasome inhibitors, PIs）作为核心治疗药物可显著改善患者预后，但自噬活性的增强会降低肿瘤细胞对PI治疗的敏感性。CRIP1水平升高可作为复发/难治性多发性骨髓瘤的生物标志物，且与患者总生存期缩短显著相关。为进一步阐明CRIP1在多发性骨髓瘤发病机制中的作用，本研究开展了转录组测序。实验设计：为探究CRIP1在多发性骨髓瘤发病机制中的功能，我们通过转染CRIP1短发夹RNA（CRIP1-shRNA）构建了CRIP1敲低的多发性骨髓瘤细胞，以无关短发夹RNA（Scramble-shRNA）作为阴性对照。本研究对KMS11-CRIP1-sh与KMS11-Scr（对照）细胞系均进行了RNA测序，每组均设置3次生物学重复以完成实验验证。