Altered Expression of MicroRNAs in the Bone Marrow of Multiple Myeloma Patients and their Relationship to Cytogenetic Aberrations

Attia, Hazem Ali; Abdelrahman, Amany H.; Eid, Maha M.; Eid, Ola M.; Sallam, Mohamed T.H.; Gammal, Mosaad M. El; Kamel, Mahmoud M.

doi:10.2174/1389201021666200320135139

Cited by 4 publications

(4 citation statements)

References 18 publications

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“…A wide array of studies have revealed cytogenetic and epigenetic changes in MM cells, which influence cellular proliferation, apoptosis, autophagy, and metastasis through different mechanisms, including the regulatory effects of microRNAs (miRNAs) on the progression of MM (5). miRNAs are small single-stranded RNAs (19)(20)(21)(22) nucleotide in length), which participate in various malignant biological processes of MM (6).…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: MicroRNA-27 Inhibits Autophagy and Promotes Proliferation of Multiple Myeloma Cells by Targeting the NEDD4/Notch1 Axis

et al. 2020

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Multiple myeloma (MM) is a malignant tumor disease that seriously affects the health of patients. Previous studies have shown the crucial role of autophagy in the development of MM. Therefore, the study aimed to study the effect of miR-27 on autophagy in MM via NEDD4/Notch1 axis. RT-qPCR or western blot analysis was used to detect the expression of miR-27, NEDD4, and Notch1 in bone marrow tissues and CD138+ plasma cells of patients and MM cells. After gain- and loss-of-function assays in MM cells, proliferation and invasion were assessed by clone formation and Transwell assays. Meanwhile, expression of autophagy-related proteins was measured by western blot analysis, followed by evaluation of autophagosomes and autophagic flow. The targeting relationship was evaluated by luciferase reporter assay, whereas the binding of NEDD4 to Notch1 protein was analyzed by co-immunoprecipitation. The ubiquitination level of Notch1 protein was detected. A nude mouse tumor model was established to determine the role of miR-27 in MM in vivo . miR-27 and Notch1 upregulation and NEDD4 downregulation were observed in bone marrow tissues and CD138+ plasma cells of patients and MM cells. miR-27 negatively targeted NEDD4, while NEDD4 could specifically bind to Notch1 protein to increase Notch1 ubiquitin degradation in MM cells. miR-27 or Notch1 overexpression or NEDD4 silencing diminished autophagy but enhanced proliferation and invasion of MM cells. miR-27 upregulation promoted the formation of subcutaneous tumor in nude mice. Collectively, miR-27 elevated Notch1 expression by targeting NEDD4 and promoted the development of MM by inhibiting cell autophagy, which provides a new idea and basis for MM treatment.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: MicroRNA-27 Inhibits Autophagy and Promotes Proliferation of Multiple Myeloma Cells by Targeting the NEDD4/Notch1 Axis

et al. 2020

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“…lncRNAs regulate gene transcription activity by targeting miRNAs and have been reported to regulate physiological processes downstream, including cell viability, differentiation, apoptosis and carcinogenesis (39,40). As another type of non-coding RNA, miRNAs regulate the translation of target mRNAs by interacting with their 3'UTR (19)(20)(21). Numerous reports have confirmed that lncRNAs are miRNA sponges that indirectly affect the functions of mRNAs in multiple diseases (41,42).…”

Section: Discussionmentioning

confidence: 99%

“…MicroRNAs (miRNAs/miRs) represent a family of highly conserved RNAs that are ~22 nucleotides in length. A number of studies have demonstrated that miRNAs regulate gene expression by pairing with the 3'-untranslated regions (UTR) of target mRNAs (19)(20)(21). miRNAs serve vital roles in numerous diseases by regulating gene expression, cell proliferation, inflammation, apoptosis and invasion (22)(23)(24), such that miRNA dysregulation has been previously associated with a number of human diseases (25).…”

Section: Role Of Lncrna Part1 In Intervertebral Disc Degeneration Andmentioning

confidence: 99%

Role of lncRNA PART1 in intervertebral disc degeneration and associated underlying mechanism

et al. 2020

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Intervertebral disc degeneration (IDD) is a chronic skeletal muscle degeneration disease. Previous studies have demonstrated that long non-coding RNAs (lncRNAs) exert significant roles in serious illnesses. Prostate androgen-regulated transcript 1 (PART1) is an identified lncRNA that has been reported to be a regulator in a number of diseases. However, the potential effects of PART1 in IDD have yet to be fully elucidated. The present study aimed to investigate the roles of lncRNA PART1 in IDD and identify a possible underlying mechanism. Human nucleus pulposus (NP) cells were first exposed to lipopolysaccharide (LPS) to construct in vitro IDD models. Reverse transcription-quantitative PCR (RT-qPCR) was performed to measure lncRNA PART1 expression levels in 10 ng/ml LPS-stimulated NP cells and normal cells (untreated cells). Dual-luciferase reporter assays were conducted to verify the possible binding sites of microRNA (miR)-190a-3p on lncRNA PART1. In addition, NP cell viability and apoptosis were measured by performing MTT and flow cytometry, respectively. Expression and secretion of inflammatory factors (TNF-α, IL-1β and IL-6) and extracellular matrix (ECM) degradation-related proteins (aggrecan and collagen type II) were measured using ELISA, RT-qPCR and western blotting. Expression levels of lncRNA PART1 in LPS-treated NP cells were found to be higher compared with those in the control groups. miR-190a-3p directly targeted lncRNA PART1. PART1 knockdown enhanced cell viability, reduced cell apoptosis, inhibited inflammatory factor secretion and promoted ECM degradation in LPS-stimulated NP cells. However, transfection with the miR-190a-3p inhibitor reversed the aforementioned PART1 knockdown-induced alterations in cell viability, apoptosis, inflammatory cytokine and ECM degradation. Collectively, these results suggest that PART1 accelerates the progression of IDD by directly targeting miR-190a-3p, which provides a novel target for IDD diagnosis and treatment.

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“…It is recognized that epigenetic changes cooperate with genetic alterations to drive the malignant phenotype of MM. Specifically, aberrant DNA methylation, histone modification profiles [189][190][191][192], and abnormal microRNA (miRNA) expressions [193][194][195] have been demonstrated to be instrumental to MM pathogenesis.…”

Section: Proteasome Inhibitors and Epigenetic Drugs 371 Epigenetic Modifications As Druggable Targets In Multiple Myelomamentioning

confidence: 99%

The Landscape of Signaling Pathways and Proteasome Inhibitors Combinations in Multiple Myeloma

Paradžik

Bandini

Mereu

et al. 2021

Cancers

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Multiple myeloma is a malignancy of terminally differentiated plasma cells, characterized by an extreme genetic heterogeneity that poses great challenges for its successful treatment. Due to antibody overproduction, MM cells depend on the precise regulation of the protein degradation systems. Despite the success of PIs in MM treatment, resistance and adverse toxic effects such as peripheral neuropathy and cardiotoxicity could arise. To this end, the use of rational combinatorial treatments might allow lowering the dose of inhibitors and therefore, minimize their side-effects. Even though the suppression of different cellular pathways in combination with proteasome inhibitors have shown remarkable anti-myeloma activities in preclinical models, many of these promising combinations often failed in clinical trials. Substantial progress has been made by the simultaneous targeting of proteasome and different aspects of MM-associated immune dysfunctions. Moreover, targeting deranged metabolic hubs could represent a new avenue to identify effective therapeutic combinations with PIs. Finally, epigenetic drugs targeting either DNA methylation, histone modifiers/readers, or chromatin remodelers are showing pleiotropic anti-myeloma effects alone and in combination with PIs. We envisage that the positive outcome of patients will probably depend on the availability of more effective drug combinations and treatment of early MM stages. Therefore, the identification of sensitive targets and aberrant signaling pathways is instrumental for the development of new personalized therapies for MM patients.

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Altered Expression of MicroRNAs in the Bone Marrow of Multiple Myeloma Patients and their Relationship to Cytogenetic Aberrations

Cited by 4 publications

References 18 publications

RETRACTED: MicroRNA-27 Inhibits Autophagy and Promotes Proliferation of Multiple Myeloma Cells by Targeting the NEDD4/Notch1 Axis

RETRACTED: MicroRNA-27 Inhibits Autophagy and Promotes Proliferation of Multiple Myeloma Cells by Targeting the NEDD4/Notch1 Axis

Role of lncRNA PART1 in intervertebral disc degeneration and associated underlying mechanism

The Landscape of Signaling Pathways and Proteasome Inhibitors Combinations in Multiple Myeloma

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