RNA interference for multiple myeloma therapy: targeting signal transduction pathways

Guo, Jianfeng; McKenna, Sharon L.; O’Dwyer, Michael; Cahill, Mary R.; O’Driscoll, Caitriona M.

doi:10.1517/14728222.2015.1071355

Cited by 15 publications

(9 citation statements)

References 100 publications

(142 reference statements)

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“…The results of this previous study indicated that LNA-i-miR-221 harbored a short half-life, optimal tissue bioavailability and minimal urine excretion in mice and monkeys and revealed no toxicity in the pilot monkey study. Therefore, miRNA-based therapy is a promising novel therapeutic method for MM ( 100 , 101 ).…”

Section: Mirna-based Therapeutic Strategies In MMmentioning

confidence: 99%

The potential function of microRNAs as biomarkers and therapeutic targets in multiple myeloma (Review)

Zhu

Chu

et al. 2018

Oncol Lett

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Multiple myeloma (MM), accounting for ~1% of all types of human cancer and 13% of all hematological malignancies, is characterized by the malignant proliferation of monoclonal plasma cells (PCs) in the bone marrow. MM leads to end stage organ impairment, including bone lesions, renal dysfunction, hypercalcemia and anemia. So far, the specific pathogenesis of MM remains unclear and no early-stage sensitive biomarker of MM has been well characterized. Furthermore, treating MM is difficult, as the majority of patients eventually relapse or become refractory following treatment using presently available methods. To date, a number of studies have demonstrated that microRNAs (miRNAs) may serve crucial functions in the progression of numerous cancers, including MM. During the tumorigenesis and pathogenesis of MM, there are multiple carcinogenic events that involve the pernicious transformation from normal to malignant PCs. miRNAs, as oncogenes or tumor suppressors, regulate MM progression-related signaling pathways. In the present review, the up-to-date preliminary basic studies and associated clinical works on the underlying mechanisms of aberrant miRNA profiling in MM have been summarized, including an evaluation of its value as a potential biomarker and a novel therapeutic strategy for MM.

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Section: Mirna-based Therapeutic Strategies In MMmentioning

confidence: 99%

The potential function of microRNAs as biomarkers and therapeutic targets in multiple myeloma (Review)

Zhu

Chu

et al. 2018

Oncol Lett

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“…Different signal pathways are involved in the development and drug-resistance of MM, including PI3K/AKT/mTOR, RAS/RAF/MEK/ERK, JAK/STAT, WNT/β-catenin and NF-κB [25]. The binding of MM cells to BM stromal cells triggers adhesion- and cytokine-mediated MM cell growth, survival and migration through activation of p42/p44 MAPK [26].…”

Section: Introductionmentioning

confidence: 99%

CircRNA circ_0000190 inhibits the progression of multiple myeloma through modulating miR-767-5p/MAPK4 pathway

Feng

Zhang

et al. 2019

J Exp Clin Cancer Res

104

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BackgroundMultiple myeloma (MM) accounts for 10% of all hematological malignancies. Dysregulation of microRNAs (miRNAs) or long non-coding RNAs (lncRNAs) has important impacts on progression of MM. Circular RNAs (circRNAs) are correlated with malignancy in the modulation of tumor progression. This study aims to investigate the effect of circ_0000190 on regulating the progression of MM.MethodMicroscopic examination via single molecule fluorescent in situ hybridization indicates the location of circ_0000190. qRT-PCR and Western blot were used to evaluate the expression of RNAs and proteins. Potential target of circ_0000190 was searched as miRNA, and examined by luciferase reporter assay. A computational screen was also conducted to search the potential target of miRNA. In vitro cell viability, proliferation, apoptosis assays and flow cytometric were performed to assess the effects of circ_0000190 and its target on MM. Mice model of human MM was established with subcutaneous xenograft tumor, qRT-PCR and western blot were performed to detect the underlying mechanisms of circ_0000190 on MM.ResultsCirc_0000190 was located in the cytoplasm, and down-regulated in both bone marrow tissue and peripheral blood, while the target of circ_0000190, miR-767-5p, was up-regulated, suggesting a negative correlation between them. The binding ability between circ_0000190 and miR-767-5p was confirmed by luciferase reporter assay. Moreover, circ_0000190 inhibited cell viability, proliferation and induced apoptosis of MM thus inhibiting cell progression, which is partially through the negative regulation of miR-767-5p. Mitogen-activated protein kinase 4 (MAPK4) is a direct target of miR-767-5p. In addition, over-expression of miR-767-5p promoted cell progression by directly targeting and regulating MAPK4. The MM model mice with administration of circ_0000190 suppressed tumor growth and progression.ConclusionOur results revealed that the ability of circ_0000190 to protect against MM was inherited through repression of miR-767-5p, and miR-767-5p might be a tumor drive through targeting MAPK4. Therefore, a novel role of circ_0000190 on regulating the progression of MM was found, and the clinical application of circRNAs might represent a strategy in MM.Electronic supplementary materialThe online version of this article (10.1186/s13046-019-1071-9) contains supplementary material, which is available to authorized users.

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“…However, M protein classification cannot cover all patients with MM and this disease has been found to have a great heterogeneity at the genetic level. Therefore, researchers have focused on the field of genetic molecular research as regards MM in the hope of identifying novel individualized biomarkers and treatment for this disease (4,5).…”

Section: Introductionmentioning

confidence: 99%

Serum miR-30d as a novel biomarker for multiple myeloma and its antitumor role in U266 cells through the targeting of the MTDH/PI3K/Akt signaling pathway

et al. 2018

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Multiple myeloma (MM) is a hematological tumor and is characterized by the infiltration of malignant clonal plasma cells (PCs) in bone marrow. MicroRNAs (miRNAs or miRs) have been reported to play an important role in the genesis and progression of MM. However, little is known about the clinical diagnostic value and biological functions of miR-30d in MM. In this study, to investigate the role of miR-30d in MM, we used reverse transcription-quantitative polymerase chain reaction quantitative (RT-qPCR) to detect the relative expression level of miR-30d in the serum of 81 patients with primary MM and 78 healthy donors (HDs). The biological functions of miR-30d were then assessed by CCK-8 assay, flow cytometric analysis of apoptosis and western blot (WB) analysis in U266 cells. Moreover, the confirmation of the target gene of miR-30d was conducted by luciferase reporter assay. Our results indicated that miR-30d expression was significantly downregulated in the serum of patients with primary MM compared with that of the HDs and that it was significantly associated with several clinical indicators of MM. Further cell functional analyses using the U266 cells revealed that miR-30d functions as a tumor suppressor gene in MM by inhibiting cell viability and promoting cell apoptosis. Moreover, miR-30d was confirmed to directly bind to the 3'UTR of its target gene, metadherin (MTDH) and inhibit the activation of the downstream PI3K/Akt signaling pathway. On the whole, the findings of this study indicate that the serum expression level of miR-30d is of great significance to the diagnosis and treatment monitoring of patients with MM. Moreover, miR-30d carries out its antitumor role in U266 cells through the inhibition of the activation of the PI3K/Akt signaling pathway by negatively regulating MTDH, which reveals its potential for use as a therapeutic target for MM.

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RNA interference for multiple myeloma therapy: targeting signal transduction pathways

Cited by 15 publications

References 100 publications

The potential function of microRNAs as biomarkers and therapeutic targets in multiple myeloma (Review)

The potential function of microRNAs as biomarkers and therapeutic targets in multiple myeloma (Review)

CircRNA circ_0000190 inhibits the progression of multiple myeloma through modulating miR-767-5p/MAPK4 pathway

Serum miR-30d as a novel biomarker for multiple myeloma and its antitumor role in U266 cells through the targeting of the MTDH/PI3K/Akt signaling pathway

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