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Cited by 82Multiple Myeloma Research and TreatmentsMicroRNA in disease regulationChronic Lymphocytic Leukemia Research

Investigational agent MLN9708/2238 targets tumor-suppressor miR33b in MM cells

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Tian, Ze, Zhao, Jian-jun, Tai, Yu-Tzu, Amin, Samir B., Hu, Yiguo, Berger, Allison J., Richardson, Paul, Chauhan, Dharminder +1 more·2012·Blood
DOI 10.1182/blood-2012-01-401794PMC PMC3496955
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Abstract

miRs play a critical role in tumor pathogenesis as either oncogenes or tumor-suppressor genes. However, the role of miRs and their regulation in response to proteasome inhibitors in multiple myeloma (MM) is unclear. In the current study, miR profiling in proteasome inhibitor MLN2238-treated MM.1S MM cells shows up-regulation of miR33b. Mechanistic studies indicate that the induction of miR33b is predominantly via transcriptional regulation. Examination of miR33b in patient MM cells showed a constitutively low expression. Overexpression of miR33b decreased MM cell viability, migration, colony formation, and increased apoptosis and sensitivity of MM cells to MLN2238 treatment. In addition, overexpression of miR33b or MLN2238 exposure negatively regulated oncogene PIM-1 and blocked PIM-1 wild-type, but not PIM-1 mutant, luciferase activity. Moreover, PIM-1 overexpression led to significant abrogation of miR33b- or MLN2238-induced cell death. SGI-1776, a biochemical inhibitor of PIM-1, triggered apoptosis in MM. Finally, overexpression of miR33b inhibited tumor growth and prolonged survival in both subcutaneous and disseminated human MM xenograft models. Our results show that miR33b is a tumor suppressor that plays a role during MLN2238-induced apoptotic signaling in MM cells, and these data provide the basis for novel therapeutic strategies targeting miR33b in MM.

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  • miR-33b-5p is predominantly upregulated in multiple myeloma after proteasome inhibitor treatment.

    “It drew our attention that miR-33b-5p was predominantly upregulated in multiple myeloma post treatment with proteasome inhibitor (15, 16).”

    From miR-33b-3p Acts as a Tumor Suppressor by Targeting DOCK4 in Prostate Cancer (2021) · cites this paper as [16]

    The section “MLN2238 induces miR33b and MM patient tumor cells express low constitutive levels of miR33b” reports that miR33b was among the most upregulated miRNAs after MLN2238 treatment of multiple myeloma cell lines (page unavailable). The paper calls it miR33b, not specifically miR-33b-5p, and tests the proteasome inhibitor MLN2238 rather than proteasome inhibitors generally. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Tian, Z., Zhao, J.-J., Tai, Y.-T., Amin, S. B., Hu, Y., Berger, A. J., Richardson, P., Chauhan, D., & Anderson, K. C.
Affiliations
  • Harvard University (US)
  • Dana-Farber Cancer Institute (US)
  • LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; and
  • Takeda Oncology (United States) (US)
ORCID
Venue
Blood
Publisher
American Society of Hematology
Published
2012-11-08
Volume
120
Issue
19
Pages
3958-3967
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood-2012-01-401794
PMC
PMC3496955
OpenAlex
W2045999249
Cited by
82
References
3
Citations by year
2026: 1 · 2025: 1 · 2024: 4 · 2023: 4 · 2022: 4 · 2021: 9 · 2020: 6 · 2019: 9 · 2018: 5 · 2017: 6 · 2016: 5 · 2015: 6 · 2014: 10 · 2013: 12
FWCI
5.97
Type
journal article
Language
en
Open access
Locations
  • Blood (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5p01ca078378-15, P50-100707, PO1-CA078378)
  • U.S. Public Health Service (P50100707)
  • National Cancer Institute (P01-CA078378, P50CA100707, R01CA050947)
Topics
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
Keywords
multiple myeloma, proteasome inhibitors, PIM-1, tumor suppressor microRNA, apoptosis, transcriptional regulation of microRNA, SGI-1776, xenograft tumor growth
MeSH terms
Animals, Antineoplastic Agents, Boron Compounds, Cell Movement, Cell Survival, Glycine, Humans, Imidazoles, Multiple Myeloma, Pyridazines, Signal Transduction, Gene Expression Regulation, Neoplastic, Cluster Analysis, Genes, Tumor Suppressor, Cell Death, Drug Resistance, Neoplasm, Gene Expression Profiling, Xenograft Model Antitumor Assays, MicroRNAs, Cell Line, Tumor, Mice, Proto-Oncogene Proteins c-pim-1

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