ArticleProtein & cell2018
Pirh2 mediates the sensitivity of myeloma cells to bortezomib via canonical NF-κB signaling pathway.
Article in Protein & cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- Single-cell profiling reveals MIF-mediated immune evasion and CD8 + T cell exhaustion in relapsed multiple myeloma.Clinical and experimental medicine · 2026Article
- Regulatory role of E3 ubiquitin ligases in multiple myeloma: from molecular mechanisms to therapeutic strategies.Frontiers in cell and developmental biology · 2025Review
- Acquired Bortezomib Resistance in Multiple Myeloma: From Mechanisms to Strategy.Current treatment options in oncology · 2024Review
- Factors determining the sensitivity to proteasome inhibitors of multiple myeloma cells.Frontiers in pharmacology · 2024Review
- Mechanisms underlying synergism between circularized tumor necrosis factor-related apoptosis inducing ligand and bortezomib in bortezomib-sensitive or -resistant myeloma cells.Hematological oncology · 2022Article
- The Role of E3 Ligase Pirh2 in Disease.Cells · 2022Review
- NEDD4L binds the proteasome and promotes autophagy and bortezomib sensitivity in multiple myeloma.Cell death & disease · 2022Article
- Proteasomal Degradation of Zn-Dependent Hdacs: The E3-Ligases Implicated and the Designed Protacs That Enable Degradation.Molecules (Basel, Switzerland) · 2021Review
- Research progress in proteasome inhibitor resistance to multiple myeloma.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2021Article
- The RNA-binding protein HuR is a novel target of Pirh2 E3 ubiquitin ligase.Cell death & disease · 2021Article
- Expression and correlation of IL-2, IL-10 and TNF-α in patients with multiple myeloma-infected herpes zoster treated by bortezomib-containing regimen.American journal of translational research · 2021Article
- Water-separated part of Chloranthus serratus alleviates lipopolysaccharide- induced RAW264.7 cell injury mainly by regulating the MAPK and Nrf2/HO-1 inflammatory pathways.BMC complementary and alternative medicine · 2019Article
- Anxiolytic effects of polydatin through the blockade of neuroinflammation in a chronic pain mouse model.Molecular painArticle
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clinical success of the proteasome inhibitor established bortezomib as one of the most effective drugs in treatment of multiple myeloma (MM). While survival benefit of bortezomib generated new treatment strategies, the primary and secondary resistance of MM cells to bortezomib remains a clinical concern. This study aimed to highlight the role of p53-induced RING-H2 (Pirh2) in the acquisition of bortezomib resistance in MM and to clarify the function and mechanism of action of Pirh2 in MM cell growth and resistance, thereby providing the basis for new therapeutic targets for MM. The proteasome inhibitor bortezomib has been established as one of the most effective drugs for treating MM. We demonstrated that bortezomib resistance in MM cells resulted from a reduction in Pirh2 protein levels. Pirh2 overexpression overcame bortezomib resistance and restored the sensitivity of myeloma cells to bortezomib, while a reduction in Pirh2 levels was correlated with bortezomib resistance. The levels of nuclear factor-kappaB (NF-κB) p65, pp65, pIKBa, and IKKa were higher in bortezomib-resistant cells than those in parental cells. Pirh2 overexpression reduced the levels of pIKBa and IKKa, while the knockdown of Pirh2 via short hairpin RNAs increased the expression of NF-κB p65, pIKBa, and IKKa. Therefore, Pirh2 suppressed the canonical NF-κB signaling pathway by inhibiting the phosphorylation and subsequent degradation of IKBa to overcome acquired bortezomib resistance in MM cells.
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