Paeoniflorin inhibits angiogenesis in multiple myeloma by decreasing the MEF2A level - downregulate the expression of lncRNA MALAT1 within exosomes

Sep 30, 2026

Upload by Oliver

Paeoniflorin (PF) is evaluated for its ability to inhibit angiogenesis in multiple myeloma by lowering MEF2A levels and suppressing lncRNA MALAT1 expression within exosomes. Exosome cargos from clinical serum and U266 cells are profiled, and MALAT1-related signatures are verified through GEO and clinicopathological analyses. Functional assays in HUVEC cells, along with subcutaneous tumor-bearing mouse models, assess effects on tube formation and markers including VEGFA, CD31, and Ki67. Bioinformatic and experimental approaches confirm MALAT1/miR-17/VEGFA ceRNA regulation and PF interaction with MEF2A via docking, WB, and PCR.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Background

Angiogenesis in multiple myeloma

Exosomes and VEGF regulation

Methods

Exosome cargo profiling and DEG analysis

In vitro functional assays

In vivo xenograft evaluations

ceRNA and transcription factor validation

Results

MALAT1 correlates with VEGFA, CD31, and prognosis

PF blocks MALAT1-driven angiogenic effects

PF targets MEF2A and disrupts MALAT1/miR-17/VEGFA signaling

Conclusion

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Paeoniflorin inhibits angiogenesis in multiple myeloma by decreasing the MEF2A level to downregulate the expression of lncRNA MALAT1 within exosomes Jiaqi Fu1, Junqiang Wang2, Jie Zhang3, Runjie Sun3, ManyaYu1, Muyun Wu1 & Xing Cui3􀀍 Angiogenesis is a pivotal mechanism driving tumor proliferation, and the epigenetic regulation ofangiogenesis represents a cutting-edge area of current research in multiple myeloma (MM) . Highthroughput sequencing was carried out to detect the cargos of exosomes from clinical serum and U266 cells, then GSE108824 database was analyzed for the finding of differentially expressed genes (DEGs) . The intersect set was made based on the three gene sets. The clinical features of Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1)were verified through GEO and clinicopathological data analyses. Cell viability, tube formation assay, level of MALAT1 and VEGFA were used to evaluate the effect of U266 exosome pretreated with or without paeoniflorin (PF) on angiogenesis in HUVEC cells. Subcutaneous tumor-bearing mice were established by injection of U266 cells and exosomes derived from U266 cells which pretreated with or without PF. Tumor size, HE staining, analysis of MALAT1 and VEGFA levels, as well as IHC staining for VEGFA, CD31, and Ki67 were performed to evaluate the in vivo effects of PF. The interactions between MALAT1, VEGFA, and microRNAs were demonstrated by TargetScan, MiRanda databases and Luciferase reporter assay. Furthermore, network pharmacology and RROMO, Genecards, AnimalTFDB, JASPAR databases were combinedto predict transcription factors (TF) associated with MALAT1 and analyze the binding sites between PF and these transcription factors. The validation of PF effect onTF was conducted by WB and PCR. Clinical studies indicated a notable positive correlation between MALAT1 level and VEGFA, CD31 expression, moreover, the high MALAT1 level is closely related to poor prognosis of MM. We demonstrated that MALAT1 was the highest expression linear RNA in U266 exosomes and could be transported to HUVEC cells through exosomes, promoting HUVEC cells differentiation and angiogenesis by stimulating VEGFA expression. The tube formation could be blocked if we knockdown the MALAT1 in U266 exosome. It was also proved that this pathological process can be blocked by PF in vitro and in vivo experiments. The ceRNA mechanism in MALAT1/miR-17/VEGFA was predicted and then confirmed by luciferase reporter assay. 2548 PF target genes were retrieved from databases, and the intersections with MALAT1-related differentially expressed proteins, mRNA and TF gene were identified Venn diagaram. MEF2A binding sites were predicted JASPAR, finally molecular docking showed strong affinity between PF and MEF2A (-16.5 kcal/mol).Then the effect of PF on MEF2A/MALAT1 was confirmed by WB or PCR test. To summarize, our study revealed that myeloma cells can increase angiogenesis by releasing exosome to influence the endothelial cells. The MALAT1 from myeloma cells is the crucial factor in this pathological process. PF can obstruct this process by intervening in the MEF2A/MALAT1 in myeloma cells. Keywords MALAT1, MEF2A, Exosome, Paeoniflorin, Angiogenesis, Multiple myeloma 1The First School of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China. 2Department of Gerontology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine/Shandong Hospital of Integrated Traditional Chinese and Western Medicine, Jinan, China. 3Center of Oncology and Hematology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine/ Shandong Hospital of Integrated Traditional Chinese and Western Medicine, 1 Jingba Road, Jinan 250001, China. 􀀍 email: [cdz45@foxmail.com](cdz45@foxmail.com) [www. nature.com/scientificreports/](www. nature.com/scientificreports/) Multi

FAQs

How does paeoniflorin affect angiogenesis in multiple myeloma?

PF inhibits angiogenesis by reducing MEF2A levels and downregulating lncRNA MALAT1 expression within exosomes, leading to reduced VEGFA-driven endothelial functions.

What role does MALAT1 play in the study?

MALAT1 is identified as highly expressed in U266 exosomes and is transported to endothelial cells, where it promotes differentiation and angiogenesis by stimulating VEGFA expression.

Which signaling mechanism is proposed for MALAT1’s regulation of angiogenesis?

The study predicts and confirms a ceRNA mechanism involving MALAT1/miR-17/VEGFA, supported by luciferase reporter assays.

Sep 30, 2026

Upload by Oliver