The importance of angiogenesis in multiple myeloma (MM) is unquestionable; however, to date, the success of antiangiogenic therapies has been fairly limited. Exosomal circular RNAs (circRNAs) have been proven to be pivotal players in angiogenesis in various cancers. Nevertheless, their role in MM remains unknown. Therefore, we aimed to identify differentially expressed circRNAs in peripheral blood exosomes from MM patients and explore their diagnostic and prognostic values. We screened 2,052 circRNAs with significant differential expression between MM patients and healthy controls via high-throughput sequencing. qRT-PCR confirmed that the expression of circ-ATP10A was significantly increased in MM patients. The bioinformatics analyses suggested that circ-ATP10A can act as a microRNA (miRNA) sponge and regulate the expression of downstream vascular endothelial growth factor-B (VEGFB), hypoxia-inducible factor-1alpha (HIF1A), platelet-derived growth factor subunit A (PDGFA), and fibroblast growth factor (FGF). The immunohistochemical results indicated that the circ-ATP10A level was positively correlated with the protein levels of VEGFB and marrow microvessel density (MVD) in MM patients, and the receiver operating characteristic (ROC) curve, area under the ROC curve (AUC) and Kaplan-Meier survival curve analyses confirmed it as a prognostic biomarker. Collectively, our study indicates that exosomal circ-ATP10A is a valuable prognostic biomarker in MM and may promote MM angiogenesis by targeting hsa-miR-6758-3p/hsa-miR-3977/hsa-miR-6804-3p/hsa-miR-1266-3p/hsa-miR-3620-3p and modulating their downstream mRNAs, such as VEGFB, HIF1A, PDGF, and FGF.
Background Bortezomib-induced peripheral neuropathy (BiPN) is a common complication of multiple myeloma (MM) treatment that seriously affects the quality of life of patients. The purpose of the present study was to explore the therapeutic effect of paeoniflorin on BiPN and its possible mechanism. Methods ELISA was used to measure the level of interleukin-6 (IL6) in the plasma of MM patients, and bioinformatics analysis was used to predict the mechanism underlying the effect of paeoniflorin on peripheral neuropathy. Cell and animal models of BiPN were constructed to evaluate mitochondrial function by measuring cell viability and mitochondrial quality and labeling mitochondria with MitoTracker Green. Nerve injury in mice with BiPN was assessed by behavioral tests, evaluation of motor nerve conduction velocity, hematoxylin-eosin (HE) staining, electron microscopy and analysis of the levels of reactive oxygen species (ROS). Western blotting and immunohistochemistry (IHC) were used to assess the expression of autophagy-related proteins. Results In MM patients, IL6 levels were positively correlated with the degree of PN. The results of bioinformatics analysis suggested that paeoniflorin ameliorated PN by altering inflammation levels and mitochondrial autophagy. Paeoniflorin increased PC12 cell viability and mitochondrial autophagy levels, alleviated mitochondrial damage, and reduced IL6 levels. In addition, paeoniflorin effectively improved the behavior of mice with BiPN, relieved sciatic nerve injury in mice, increased the expression of LC3II/I, beclin-1, and Parkin in sciatic nerve cells, and increased the expression of LC3B and Parkin in the nerve tissue. Conclusion The present study confirmed that paeoniflorin significantly ameliorated peripheral neuropathy (PN) caused by bortezomib, possibly by reducing IL6 levels to regulate PARKIN-mediated mitochondrial autophagy and mitochondrial damage.
Introduction: N1‑methyladenosine (m1A), a methylation modification on RNA, is gaining attention for its role across diverse biological processes. However, the potential roles of m1A regulator-mediated methylation modification in multiple myeloma (MM) remain unclear.Methods: We investigated the mRNA expression of m1A regulators in normal plasma (NP, n = 9) and MM (n = 174) bone marrow plasma cells and comprehensively evaluated the m1A modification patterns of 559 MM samples based on the expression of 10 m1A-related regulatory genes. A univariate Cox regression model, Kaplan–Meier survival curve, unsupervised clustering and gene enrichment analysis were used to explore the associations between m1A‑related regulatory genes and MM patient survival and prognosis. Additionally, the m1Ascore was constructed to quantify m1A modification patterns of individual tumors using the principal component analysis algorithm.Results: Compared with NP, the expression of five genes (TRMT61A, TRMT61B, YTHDF1, YTHDF2, YTHDF3) was upregulated in MM patients. The Kaplan–Meier survival curve showed the high expression of the above five genes was associated with shorter overall survival. Three distinct m1A modification patterns were determined, of which cluster B showed the worst outcome; the expression of ALKBH3, YTHDF2, TRMT10C, TRMT6, and TRMT61B was high and the expression of ALKBH1 and YTHDC1 was low in cluster B. In addition, the relationships between the m1Ascore and survival, m1Aclusters, m1A gene clusters, and PD-L1 expression all indicated that high m1Ascore was associated with clinical benefits and therapeutic advantages.Conclusion: These findings indicate that m1A‑related regulatory genes play a crucial role in regulating MM progression and that the m1Ascore could be used for diagnostic and prognostic purposes.
Background:MM is still an incurable disease and osteoclast-mediated bone destruction is a hallmark. Existing agents effectively reduce the number of osteoclasts (OCs) and prevent bone-related diseases but have little effect on overall survival. Investigating the potential mechanisms and developing novel agents against bone lesions is essential.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.