Whole transcriptome sequencing and integrated network analysis elucidates the effects of 3, 8-Di-O-methylellagic acid 2-O-glucoside derived from Sanguisorba offcinalis L., a novel differentiation inducer on erythroleukemia cells. (April 2021)

• Record Type: Journal Article
• Authors: Long, Wang; Liu, Sha; Li, Xiao-Xuan; Shen, Xin; Zeng, Jing; Luo, Jie-Si; Li, Ke-Ru; Wu, An-Guo; Yu, Lu; Qin, Da-Lian; Hu, Guang-Qiang; Yang, Jing; Wu, Jian-Ming
• Is Part Of: Pharmacological research. Volume 166(2021)
• Publication Date: 2021-04
• Subjects: 3, 8-Di-O-methylellagic acid 2-O-glucoside (PubChem CID: 75253873) -- 3-O-methylellagic acid (PubChem CID: 13915428) -- Ellagic acid (PubChem CID: 5281855); AEL acute erythroid leukemia -- AML acute myeloid leukemia -- MDS myelodysplastic syndrome -- OS overall survival -- ICT intensive chemotherapy -- BMT bone marrow transplantation -- ATRA all-trans-retinoic acid -- MEP megakaryocyte-erythroid progenitor -- EPO erythropoietin -- TPO thrombopoietin -- ncRNAs noncoding RNAs -- miRNAs microRNAs -- lncRNAs long noncoding RNAs -- circRNAs circular RNAs -- S. officinalis Sanguisorba officinalis L -- DMAG 3, 8-Di-O-methylellagic acid 2-O-glucoside -- TCMSP Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform -- CCK-8 Cell Counting Kit-8 -- PBS phosphate buffer saline -- DAPI diamidino-2-phenylindole -- GO Gene Ontology -- KEGG Kyoto Encyclopedia of Genes and Genomes -- RT-qPCR Quantitative real-time PCR -- UPLC-QTOF MS ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry -- CC cellular components -- BP biological processes -- MF molecular function -- APL acute promyelocytic leukemia -- T2D Type 2 diabetes -- PVT1 lncRNA Plasmacytoma variant translocation 1 -- HSCs hematopoietic stem cells -- T-ALL T-cell acute lymphoblastic leukemia -- HMAs hypomethylating agents; Acute erythroid leukemia -- 3, 8-Di-O-methylellagic acid 2-O-glucoside -- Non-coding RNAs -- Whole-transcriptome sequencing -- Differentially regulated networks; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2021.105491
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: Acute erythroid leukemia (AEL) is a rare and aggressive hematologic malignancy with no specific treatment. Sanguisorba officinalis L. ( S. officinalis ), a well-known traditional Chinese medicine, possesses potent anticancer activity. However, the active components of S. officinalis against AEL and the associated molecular mechanisms remain unknown. In this study, we predicted the anti-AML effect of S. officinalis based on network pharmacology. Through the identification of active components of S. officinalis, we found that 3, 8-Di-O-methylellagic acid 2-O-glucoside (DMAG) not only significantly inhibited the proliferation of erythroleukemic cell line HEL, but also induced their differentiation to megakaryocytes. Furthermore, we demonstrated that DMAG could prolong the survival of AEL mice model. Whole-transcriptome sequencing was performed to elucidate the underlying molecular mechanisms associated with anti-AEL effect of DMAG. The results showed that the total of 68 miRNAs, 595 lncRNAs, 4030 mRNAs and 35 circRNAs were significantly differentially expressed during DMAG induced proliferation inhibition and differentiation of HEL cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the differentially expressed miRNAs, lncRNAs, mRNAs and circRNAs were mainly involved in metabolic, HIF-1, MAPK, Notch pathway and apoptosis. The co-expression networks showed that miR-23a-5p, miR-92a-1–5p, miR-146b and miR-760 regulatory networks were crucial for megakaryocyte differentiation induced by DMAG. In conclusion, our results suggest that DMAG, derived from S. officinalis might be a potent differentiation inducer of AEL cells and provide important information on the underlying mechanisms associated with its anti-AEL activity. Graphical Abstract: ga1