Significance of a tumor microenvironment-mediated P65-miR-30a-5p-BCL2L11 amplification loop in multiple myeloma

Xie, Lingling; Wei, Jinhong; Gao, Zhihua; Huang, Hongming; Ju, Shaoqing; Wang, Xudong

doi:10.1016/j.yexcr.2022.113113

Cited by 5 publications

(2 citation statements)

References 28 publications

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“…Zhong and colleagues confirmed that miR-98-5p promoted COL1A2 inducing extracellular matrix deposition and contributing to asthma pathogenesis in human (Zhong et al, 2022). Additionally, miR-30a-5p was detected to down-regulate BCL2L11 depending on P65 for aggravating multiple myeloma (Xie et al, 2022). In Cluster 2, miR-106b-5p is a hub node.…”

Section: Discussionmentioning

confidence: 91%

mRNA and lncRNA co-expression network in mice of acute intracerebral hemorrhage

Cai

et al. 2023

Front. Mol. Neurosci.

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BackgroundIntracerebral hemorrhage (ICH) is a severe subtype of stroke lacking effective pharmacological targets. Long noncoding RNA (lncRNA) has been confirmed to participate in the pathophysiological progress of various neurological disorders. However, how lncRNA affects ICH outcomes in the acute phase is not completely clear. In this study, we aimed to reveal the relationship of lncRNA-miRNA-mRNA following ICH.MethodWe conducted the autologous blood injection ICH model and extracted total RNAs on day 7. Microarray scanning was used to obtain mRNA and lncRNA profiles, which were validated by RT-qPCR. GO/KEGG analysis of differentially expressed mRNAs was performed using the Metascape platform. We calculated the Pearson correlation coefficients (PCCs) of lncRNA-mRNA for co-expression network construction. A competitive endogenous (Ce-RNA) network was established based on DIANALncBase and miRDB database. Finally, the Ce-RNA network was visualized and analyzed by Cytoscape.ResultsIn total, 570 differentially expressed mRNAs and 313 differentially expressed lncRNAs were identified (FC ≥ 2 and value of p <0.05). The function of differentially expressed mRNAs was mainly enriched in immune response, inflammation, apoptosis, ferroptosis, and other typical pathways. The lncRNA-mRNA co-expression network contained 57 nodes (21 lncRNAs and 36 mRNAs) and 38 lncRNA-mRNA pairs. The ce-RNA network was generated with 303 nodes (29 lncRNAs, 163 mRNAs, and 111 miRNAs) and 906 edges. Three hub clusters were selected to indicate the most significant lncRNA-miRNA-mRNA interactions.ConclusionOur study suggests that the top differentially expressed RNA molecules may be the biomarker of acute ICH. Furthermore, the hub lncRNA-mRNA pairs and lncRNA-miRNA-mRNA correlations may provide new clues for ICH treatment.

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Section: Discussionmentioning

confidence: 91%

mRNA and lncRNA co-expression network in mice of acute intracerebral hemorrhage

Cai

et al. 2023

Front. Mol. Neurosci.

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“… 31 Furthermore, the downregulated genes included 2 genes associated with posttranscriptional ( MIR30A ) or transcriptional ( MYB ) regulation ( Table 1 ). MIR30A is reportedly a RELA target gene in MM, 32 and in mice, c-MYB is required for enabling long-lived PCs to home to the BM by responding to chemokines. 33 Several categories including metabolism, intracellular trafficking/transport, and cytoskeleton-associated genes comprised a number of genes that were downregulated or upregulated upon shRELA knockdown, ( Table 1 ; supplemental Table 3 ).…”

Section: Resultsmentioning

confidence: 99%

Cytokine receptor IL27RA is an NF-κB–responsive gene involved in CD38 upregulation in multiple myeloma

et al. 2023

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Multiple myeloma (MM) shows constitutive activation of canonical and non-canonical nuclear factor-ĸB (NF-ĸB) signaling through genetic mutations or stimuli from the tumour microenvironment (TME). A subset of MM cell lines showed dependency for cell growth and survival on the canonical NF-ĸB transcription factor RELA alone, suggesting a critical role for a RELA-mediated biological program in MM pathogenesis. Here, we determined the RELA-dependent transcriptional program in MM cell lines and found the expression of the cell surface molecules IL-27 receptor-α (IL-27Rα) and the adhesion molecule JAM2 to be responsive to RELA at the mRNA and protein levels. IL-27Rα and JAM2 were expressed on primary MM cells at higher levels than on normal long-lived plasma cells (PCs) in the bone marrow. IL-27 activated STAT1, and to a lesser extent STAT3, in MM cell lines and in PCs generated from memory B-cells in an IL-21-dependent in vitro PC-differentiation assay. Concomitant activity of IL-21 and IL-27 enhanced differentiation into PCs and increased cell-surface expression of the known STAT target gene CD38. In accordance, a subset of MM cell lines and primary MM cells cultured with IL-27 upregulated CD38 cell-surface expression, a finding with potential implications for enhancing the efficacy of CD38-directed monoclonal antibody (mAb) therapies by increasing CD38-expression on tumour cells. The elevated expression of IL-27Rα and JAM2 on MM cells compared to normal PCs may be exploited for the development of targeted therapeutic strategies that modulate the interaction of MM cells with the TME.

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Noncoding RNAs in the crosstalk between multiple myeloma cells and bone marrow microenvironment

Tang

2023

Cancer Letters

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Significance of a tumor microenvironment-mediated P65-miR-30a-5p-BCL2L11 amplification loop in multiple myeloma

Cited by 5 publications

References 28 publications

mRNA and lncRNA co-expression network in mice of acute intracerebral hemorrhage

mRNA and lncRNA co-expression network in mice of acute intracerebral hemorrhage

Cytokine receptor IL27RA is an NF-κB–responsive gene involved in CD38 upregulation in multiple myeloma

Noncoding RNAs in the crosstalk between multiple myeloma cells and bone marrow microenvironment

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