Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exosomes are small endosome-derived vesicles containing a wide range of functional proteins, mRNA, and miRNA. Exosomal miRNA from cancer cells helps modulate the microenvironment. In multiple myeloma (MM), the massive proliferation of malignant plasma cells causes hypoxia. To date, the majority of in vitro hypoxia studies of cancer cells have used acute hypoxic exposure (3-24 hours). Thus, we attempted to clarify the role of MM-derived exosomes in hypoxic bone marrow by using MM cells grown continuously in vitro under chronic hypoxia (hypoxia-resistant MM [HR-MM] cells). The HR-MM cells produced more exosomes than the parental cells under normoxia or acute hypoxia conditions, and miR-135b was significantly upregulated in exosomes from HR-MM cells. Exosomal miR-135b directly suppressed its target factor-inhibiting hypoxia-inducible factor 1 (FIH-1) in endothelial cells. Finally, exosomal miR-135b from HR-MM cells enhanced endothelial tube formation under hypoxia via the HIF-FIH signaling pathway. This in vitro HR myeloma cell model will be useful for investigating MM cell-endothelial cell interactions under hypoxic conditions, which may mimic the in vivo bone marrow microenvironment. Although tumor angiogenesis is regulated by various factors, exosomal miR-135b may be a target for controlling MM angiogenesis.
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PMID:Exosomal miR-135b shed from hypoxic multiple myeloma cells enhances angiogenesis by targeting factor-inhibiting HIF-1. 2549 51

Multiple myeloma (MM)is a kind of plasma tumor originated from B cell line. Its incidence ranks in second place of hematopoietic malignancies. Although continued progress was made in treatment of MM,the survival rate and prognosis of MM patients are still not satisfactory. Further understanding of the pathogenesis of MM may provide information to develop new treatment strategies, so as to improve survival rate and ameliorate its prognosis. Many researches have demonstrated that bone marrow microenvironment plays an important role in MM pathogenesis, which regulates the biological properties of MM cells, including migration and proliferation, through miRNA, mRNA and protein contained in the exosomes released from the cells in the tumor microenvironment. Recently, as the tumor suppressor genes and oncogenes, exosomal microRNA become a hot spot in research. Compared with those of the normal ones, exosomes in MM have less miR-15a and/or more miR-135b and miR-21. These differences will accelerate the progression of MM via PI3K/Akt/eNOS/VEGF pathway, FIH-HIF pathway, MAPK/ERK/Ras pathway and so on, that are expected to become the new targets for the treatment of MM. This review summarizes the role and the possible mechanism of exosomes in the progression of MM.
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PMID:[Role of Exosomal miRNA in Multiple Myeloma Progression and Its Possible Mechanism -Review]. 2824 21