Myeloma cell adhesion to bone marrow stromal cells confers drug resistance by microRNA-21 up-regulation
Abstract
The bone marrow microenvironment plays a role in myeloma cell proliferation and adhesion-mediated drug resistance. In this study, we investigated microRNA-21 (miR-21) expression changes in myeloma cells that adhered to bone marrow stromal cells (BMSCs). In addition, we studied the synergistic effect of miR-21 inhibition with dexamethasone (Dex), doxorubicin (Dox), or bortezomib (Bort) on myeloma cell survival. We found that up-regulation of miR-21 expression was partially driven by nuclear factor-κB (NF-κB) signaling via myeloma cell adhesion to BMSCs. We also confirmed that RhoB is a miR-21 regulation target gene. Moreover, miR-21 inhibition combined with cytotoxic drug Dex or Dox inhibited myeloma cell survival more effectively than either treatment alone. These results suggest that the regulatory mechanisms of miR-21 expression may be a promising target for fine-tuning anti-myeloma therapy.
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Upregulation of miR-21 has been linked with doxorubicin and dexamethasone resistance in MM cells.
“For instance, the upregulation of miR-21 hasbeen linked with doxorubicin and dexamethasone resistance in MM cells.”
From Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword (2025) · cites this paper as [240]
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Environment-mediated drug resistance: A major contributor to minimal residual disease
Meads, M. B., Gatenby, R. A., & Dalton, W. S. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2714 · Cited by 892 · see citing works
Up-regulation of miR-21 by HER2/neu signaling promotes cell invasion
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Kamrani, S., Naseramini, R., Khani, P., Razavi, Z. S., Afkhami, H., Atashzar, M. R., Nasri, F., Alavimanesh, S., Saeidi, F., & Ronaghi, H. (2025) · Cancer Cell International · doi:10.1186/s12935-025-03741-x · Cited by 27 · see citing works
“Bound of BMSCs to myeloma cellsupregulates expression of miR-21 [240].”
Non-Coding RNAs in Multiple Myeloma Bone Disease Pathophysiology
Raimondi, L., De Luca, A., Giavaresi, G., Raimondo, S., Gallo, A., Taiana, E., Alessandro, R., Rossi, M., Neri, A., Viglietto, G., et al. (2020) · Non-Coding RNA · doi:10.3390/ncrna6030037 · Cited by 16 · see citing works
- Authors
- Wang, X., Li, C., Ju, S., Wang, Y., Wang, H., & Zhong, R.
- Affiliations
- Affiliated Hospital of Nantong University (CN)
- Shanghai Changzheng Hospital (CN)
- Corresponding author
- Zhong, Renqian
- Venue
- Leukemia & Lymphoma
- Publisher
- Informa UK Limited
- Published
- 2011-06-30
- Volume
- 52
- Issue
- 10
- Pages
- 1991-1998
- ISSN
- 1026-8022 (ISSN-L)
- 1042-8194
- 1029-2403
- OpenAlex
- W2052825822
- Cited by
- 103
- References
- 3
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 8 · 2023: 3 · 2022: 10 · 2021: 6 · 2020: 8 · 2019: 6 · 2018: 6 · 2017: 9 · 2016: 6 · 2015: 10 · 2014: 14 · 2013: 10 · 2012: 1
- FWCI
- 5.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Leukemia & lymphoma/Leukemia and lymphoma (publishedVersion)
- PubMed (publishedVersion)
- 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, drug resistance, miR-21, mesenchymal stem cells, cell adhesion, bone marrow microenvironment, NF-κB signaling, RhoB, dexamethasone, doxorubicin, bortezomib, combination therapy, myeloma cell survival
- MeSH terms
- Bortezomib, Bone Marrow, Boronic Acids, Cell Adhesion, Cell Survival, Dexamethasone, Doxorubicin, Humans, Multiple Myeloma, Pyrazines, Up-Regulation, Gene Expression Regulation, Neoplastic, Stromal Cells, Coculture Techniques, Drug Resistance, Neoplasm, MicroRNAs
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