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Cited by 77Multiple Myeloma Research and TreatmentsMicroRNA in disease regulationChronic Lymphocytic Leukemia Research

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Suppressing miRNA-15a/-16 expression by interleukin-6 enhances drug-resistance in myeloma cells

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Hao, Mu, Zhang, Li, An, Gang, Sui, Weiwei, Yu, Zhen, Zou, Dehui, Xu, Yan, Chang, Hong, Qiu, Lugui·2011·Journal of Hematology & Oncology
DOI 10.1186/1756-8722-4-37PMC PMC3189173
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Abstract

The bone marrow microenvironment facilitates the survival, differentiation, and proliferation of myeloma (MM) cells. This study identified that microRNA-15a and -16 expressions tightly correlated with proliferation and drug sensitivity of MM cells. miRNA-15a/-16 expression in MM cells was significantly increased after treatment with cytotoxic agents. The interaction of bone marrow stromal cells (BMSC) with MM cells resulted in decreased miRNA-15a/-16 expression and promoted the survival of the MM cells. Interleukin-6 (IL-6) produced by BMSCs suppressed the expression of miRNA-15a and 16 in a time- and dose- dependent pattern, with the suppression on miRNA-15a being more significant than on miRNA-16. miRNA-15a-transfected MM cells were found to be arrested in G1/S checkpoint, and the transfected MM cells had decreased growth and survival. In conclusion, our data suggest that via suppressing miRNA-15a and -16 expressions, IL-6 secreted by BMSCs promotes drug-resistance in myeloma cells.

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Figure 1 Bone marrow stromal cells derived from myeloma patients (MM-BMSCs) suppress apoptosis and miRNA-15a/-16 expression in MM cells. (A) MM-BMSCs inhibited apoptosis of MM cells induced by cytotoxic agent. (B) Stem-loop RT-PCR assay showed that miRNA-15a/-16 expression in MM cells was significantly increased by melphalan and bortezomib treatment. When MM cells were co-cultured with MM-BMSCs, miRNA-15a/-16 expression in MM cells was suppressed. (C & D) IL-6 decreased miRNA-15a/-16 expression in U266 and NCI-H929 cells in a time- and dose- dependent pattern.
Figure 1 Bone marrow stromal cells derived from myeloma patients (MM-BMSCs) suppress apoptosis and miRNA-15a/-16 expression in MM cells. (A) MM-BMSCs inhibited apoptosis of MM cells induced by cytotoxic agent. (B) Stem-loop RT-PCR assay showed that miRNA-15a/-16 expression in MM cells was significantly increased by melphalan and bortezomib treatment. When MM cells were co-cultured with MM-BMSCs, miRNA-15a/-16 expression in MM cells was suppressed. (C & D) IL-6 decreased miRNA-15a/-16 expression in U266 and NCI-H929 cells in a time- and dose- dependent pattern.CC BY · PubMed Central

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Research works printed but not linked: 12

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Metadata

Authors
Hao, M., Zhang, L., An, G., Sui, W., Yu, Z., Zou, D., Xu, Y., Chang, H., & Qiu, L.
Affiliations
  • Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
  • Sichuan University (CN)
  • University Health Network (CA)
Corresponding author
Qiu, Lugui
ORCID
Venue
Journal of Hematology & Oncology
Publisher
Springer Science and Business Media LLC
Published
2011-09-22
Volume
4
Issue
1
Pages
37-37
ISSN
1756-8722 (ISSN-L)
DOI
10.1186/1756-8722-4-37
PMC
PMC3189173
OpenAlex
W2148565111
Cited by
77
References
0
Citations by year
2026: 2 · 2025: 1 · 2024: 7 · 2023: 4 · 2022: 7 · 2021: 9 · 2020: 8 · 2019: 8 · 2018: 8 · 2017: 2 · 2016: 7 · 2015: 3 · 2014: 8 · 2013: 2 · 2012: 1
FWCI
2.41
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Journal of Hematology & Oncology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • TSpace (University of Toronto) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (30871095, 81172255)
  • Peking Union Medical College
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 › Hematology › Chronic Lymphocytic Leukemia Research
Keywords
interleukin-6, multiple myeloma, drug resistance, mesenchymal stem cells, bone marrow microenvironment, G1/S cell cycle arrest, cell survival, microRNA expression
MeSH terms
Antineoplastic Agents, Bone Marrow Cells, Gene Expression Regulation, Humans, Multiple Myeloma, Interleukin-6, Apoptosis, Drug Resistance, Neoplasm, MicroRNAs

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