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Cited by 26MicroRNA in disease regulationNeuroblastoma Research and TreatmentsCancer-related molecular mechanisms research

Molecular Mechanisms of Bortezomib Action: Novel Evidence for the miRNA–mRNA Interaction Involvement

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Łuczkowska, Karolina, Rogińska, Dorota, Ulańczyk, Zofia, Paczkowska, Edyta, Schmidt, Christian Andreas, Machaliński, Bogusław·2020·International Journal of Molecular Sciences
DOI 10.3390/ijms21010350PMC PMC6981510
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Abstract

Bortezomib is an anti-tumor agent, which inhibits 26S proteasome degrading ubiquitinated proteins. While apoptotic transcription-associated activation in response to bortezomib has been suggested, mechanisms related to its influence on post-transcriptional gene silencing mediated regulation by non-coding RNAs remain not fully elucidated. In the present study, we examined changes in global gene and miRNA expression and analyzed the identified miRNA–mRNA interactions after bortezomib exposure in human neuroblastoma cells to define pathways affected by this agent in this type of cells. Cell viability assays were performed to assess cytotoxicity of bortezomib. Global gene and miRNA expression profiles of neuroblastoma cells after 24-h incubation with bortezomib were determined using genome-wide RNA and miRNA microarray technology. Obtained results were then confirmed by qRT-PCR and Western blot. Further bioinformatical analysis was performed to identify affected biological processes and pathways. In total, 719 genes and 28 miRNAs were downregulated, and 319 genes and 61 miRNAs were upregulated in neuroblastoma cells treated with bortezomib. Possible interactions between dysregulated miRNA/mRNA, which could be linked to bortezomib-induced neurotoxicity, affect neurogenesis, cellular calcium transport, and neuron death. Bortezomib might exert toxic effects on neuroblastoma cells and regulate miRNA–mRNA interactions influencing vital cellular functions. Further studies on the role of specific miRNA–mRNA interactions are needed to elucidate mechanisms of bortezomib action.

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Authors
Łuczkowska, K., Rogińska, D., Ulańczyk, Z., Paczkowska, E., Schmidt, C. A., & Machaliński, B.
Affiliations
  • Pomeranian Medical University (PL)
  • Universitätsmedizin Greifswald (DE)
Corresponding author
  • Ulańczyk, Zofia
  • Machaliński, Bogusław
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2020-01-05
Volume
21
Issue
1
Pages
350
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms21010350
PMC
PMC6981510
OpenAlex
W2997690038
Cited by
26
References
1
Citations by year
2026: 2 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 5 · 2021: 9 · 2020: 5
FWCI
1.80
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Narodowe Centrum Nauki (OPUS 2016/23/N/NZ7/03363)
  • European Union Regional Development Fund, Interreg Cooperation Program V A Mecklenburg-Western Pomerania/Brandenburg/Poland for 2014–2020: No INT14 "Consolidation of cross-border cooperation through exchange of knowledge and skills in the field of modern (INT14)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Neurology › Neuroblastoma Research and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords
bortezomib, miRNA-mRNA interactions, neuroblastoma, proteasome inhibition, gene expression profiling, miRNA expression profiling, post-transcriptional regulation, neurotoxicity, neurogenesis, calcium transport, neuronal cell death, cytotoxicity
MeSH terms
Bortezomib, Antineoplastic Agents, Calcium, Cell Survival, Humans, Neuroblastoma, RNA, Messenger, Down-Regulation, Up-Regulation, Apoptosis, Computational Biology, Gene Expression Profiling, MicroRNAs, Cell Line, Tumor, Microarray Analysis, Neurogenesis, Gene Ontology

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