下调RRBP1可调节内质网应激，通过抑制GRP78的表达，减缓恶性进展，抑制多发性骨髓瘤细胞对硼替佐米的耐药性

IF 3.2 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology Pub Date : 2025-05-08 DOI:10.1016/j.molimm.2025.05.001

Jie Wang , Haipeng Jia , Sulong Lv, Xiaofen Zhang, Yanchao Duan

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引用次数: 0

摘要

据报道，核糖结合蛋白1 （RRBP1）在某些癌症中发挥调节作用。多发性骨髓瘤（multiple myeloma， MM）与预后不良及耐药有关，但其机制尚未见报道。因此，我们对其对MM细胞的作用及具体机制进行了探讨。方法采用免疫组化法检测MM组织中RRBP1和葡萄糖调节蛋白78 （GRP78）的表达水平。分别用qRT-PCR和western blot分析mRNA和蛋白的表达水平。CCK-8法检测MM细胞活力和增殖能力。流式细胞术检测细胞凋亡。Transwell法观察细胞迁移和侵袭情况。结果RRBP1和GRP78在MM组织和MM细胞中表达上调。转染sh-RRBP1可减弱MM细胞的增殖、迁移和侵袭能力。敲低RRBP1可降低MM细胞GRP78的表达，减轻内质网应激。此外，tunicamycin诱导的MM细胞凋亡通过敲低RRBP1而增强。与对照组相比，抑制RRBP1表达增加了硼替佐米耐药MM细胞的药物敏感性。此外，GRP78过表达部分地消除了sh-RRBP1对MM细胞的作用。结论本研究阐明了RRBP1基因下调对MM细胞的抑制作用，提示RRBP1可能是治疗MM的新靶点。

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Knockdown of RRBP1 regulates endoplasmic reticulum stress to mitigate malignant progression and suppress bortezomib resistance of multiple myeloma cells by inhibiting GRP78 expression

Background

Ribosome binding protein 1 (RRBP1) was reported to play a regulatory role in certain cancers. It was related to poor prognosis and drug resistance in multiple myeloma (MM), but its mechanism has not been reported before. Hence, its effect and the specific mechanism on MM cells were explored.

Methods

The expression levels of RRBP1 and Glucose-regulated protein 78 (GRP78) in MM tissues were detected by immunohistochemical assay. The expression levels of mRNA and protein were analyzed by qRT-PCR and western blot, respectively. MM cell viability and proliferation were tested by CCK-8 assay. Flow cytometry was used to detect cell apoptosis. Transwell assay was carried out to explore cell migration and invasion.

Results

The expression levels of RRBP1 and GRP78 were upregulated in MM tissues and MM cells. Transfection of sh-RRBP1 weakened the proliferation, migration and invasion abilities of MM cells. Knockdown of RRBP1 dropped GRP78 expression and diminished endoplasmic reticulum stress in MM cells. Moreover, Tunicamycin-induced apoptosis of MM cells was enhanced by RRBP1 knockdown. Compared to the control group, inhibition of RRBP1 expression increased the drug sensitivity of bortezomib-resistant MM cells. In addition, overexpression of GRP78 partially repealed the effectiveness of sh-RRBP1 on MM cells.

Conclusion

Our study elucidated the inhibitory effect of RRBP1 knockdown on MM cells, which suggested that RRBP1 might be a novel target for the therapy against MM.

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来源期刊

Molecular immunology 医学-免疫学

CiteScore

6.90

自引率

2.80%

发文量

324

审稿时长

50 days

期刊介绍： Molecular Immunology publishes original articles, reviews and commentaries on all areas of immunology, with a particular focus on description of cellular, biochemical or genetic mechanisms underlying immunological phenomena. Studies on all model organisms, from invertebrates to humans, are suitable. Examples include, but are not restricted to: Infection, autoimmunity, transplantation, immunodeficiencies, inflammation and tumor immunology Mechanisms of induction, regulation and termination of innate and adaptive immunity Intercellular communication, cooperation and regulation Intracellular mechanisms of immunity (endocytosis, protein trafficking, pathogen recognition, antigen presentation, etc) Mechanisms of action of the cells and molecules of the immune system Structural analysis Development of the immune system Comparative immunology and evolution of the immune system "Omics" studies and bioinformatics Vaccines, biotechnology and therapeutic manipulation of the immune system (therapeutic antibodies, cytokines, cellular therapies, etc) Technical developments.