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Review
. 2020 Jul-Aug;17(4):321-334.
doi: 10.21873/cgp.20192.

Identification of MicroRNAs With In Vivo Efficacy in Multiple Myeloma-related Xenograft Models

Ulrich H Weidle  1 , Adam Nopora  1
Affiliations
Review

Identification of MicroRNAs With In Vivo Efficacy in Multiple Myeloma-related Xenograft Models

Ulrich H Weidle et al. Cancer Genomics Proteomics. 2020 Jul-Aug.

Abstract

Background/aim: Multiple myeloma is a B-cell neoplasm, which can spread within the marrow of the bones forming many small tumors. In advanced disease, multiple myeloma can spread to the blood as plasma cell leukemia. In some cases, a localized tumor known as plasmacytoma is found within a single bone. Despite the approval of several agents such as melphalan, corticosteroids, proteasome inhibitors, thalidomide-based immuno-modulatory agents, histone deacetylase inhibitors, a nuclear export inhibitor and monoclonal antibodies daratuzumab and elatuzumab, the disease presently remains uncurable.

Materials and methods: In order to define new targets and treatment modalities we searched the literature for microRNAs, which increase or inhibit in vivo efficacy in multiple-myeloma-related xenograft models.

Results and conclusion: We identified six up-regulated and twelve down-regulated miRs, which deserve further preclinical validation.

Keywords: Antisense-oligonucleotides; locked nucleic acids; microRNA delivery; microRNA mimetics; multiple myeloma; review; treatment resistance.

PubMed Disclaimer

Conflict of interest statement

AN is and UHW was an employee of Roche.

Figures

Figure 1
Figure 1. Up-regulated microRNAs promoting growth of multiple myeloma xenografts in preclinical in vivo models. The miRs are displayed according to their numerical designation. The corresponding targets are displayed. BAK: Pro-apoptotic protein BAK; BAX: BCL2-associated X protein; BTG2: BTG family member 2; EGR2: early growth response protein 2; FPN1: ferroportin 1; PHLPP2: PH domain and leucine rich repeat protein phosphatase; PI3K: phosphoinosite 3-kinase; PTEN: phosphatase and tensin homolog; PUMA: p53 up-regulator of apoptosis; CDKN1B: cyclindependent kinase inhibitor 1B; CDCN1C: cyclin-dependent kinase inhibitor 1C; RHOB: RAS homolog gene family, member B.
Figure 2
Figure 2. Down-regulated miRs inhibiting growth of multiple-myeloma-related xenografts in preclinical in vivo models. The miRs are displayed according to their numerical designation. The corresponding targets are displayed. AURKA: Aurora kinase A; BCL2: B-cell lymphoma 2; BCL9: B-cell CLL/lymphoma 9; CDK6: cyclin-dependent kinase 6; c-MET: transmembrane tyeosine kinase c-MET; DDR1: discoidin domain receptor family, member 1; DNMT3A/3B: DNA methyltransferase 3A/3B; FGF1: fibroblast growth factor 1; FOXP1: forkhead box protein P1; HDAC4: histone deacetylase 4; HIF-1α: hypoxia inducible factor 1alpha; IL8: interleukin 8; MCL1: induced myeloid leukemia inducible factor 1alpha; NOTCH1: tyrosine kinase receptor notch 1; NFĸB: nuclear factor ĸB; PTEN: phosphatase and tensin homolog; PSMβ5: proteasome subunit β type 5; USP5: uniquitin specific peptidase 25; VEGF-A: vascular endothelial growth factor-A.
Figure 3
Figure 3. miRs involved in resistance to bortezomib, dexamethasone and melphalan in preclinical in vivo models of multiple myeloma. Up-regulation of miR-155 mediates bortezomib resistance, whereas down-regulation of miR-221/222 is involved in dexamethasone and melphalan resistance. ATG12: Autophagy-related 12; Dex: dexamethasone; LAT1: large neutral amino transporter 1; MRP1: multidrug resistance associated protein 1; PSMβ5: proteasome subunit β type 5; PUMA: p53 up-regulated modulator of apoptosis; SCL7A5: solute carrier family 7, member 5.
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