title: Re-expression of microRNA-150 induces EBV-positive Burkitt lymphoma differentiation by modulating c-Myb in vitro.
abstract: Burkitt lymphoma (BL) is a highly aggressive B-cell lymphoma that includes two forms of BL differing in Epstein-Barr virus (EBV) infection status, EBV-positive and EBV-negative. Although many efforts, such as high-intensity, short-duration combination chemotherapy, have been devoted to improving therapy for this rapidly proliferating neoplasm, there are still significant treatment-associated toxicities. Therefore, there remains a need for novel effective therapeutic strategies. MicroRNAs play a role in "fine tuning" the physiological and pathological differentiation process, by which cells can rapidly regulate dynamic events such as cell-lineage decisions and morphogenesis. This unique miRNA feature shifts the traditional one drug target paradigm to a novel one drug multiple targets paradigm. Here, we found that BL cell lines showed an extremely low expression of microRNA-150 (miR-150), and then restored miR-150 expression at physiologic levels in BL cell lines Daudi, Raji, BJAB, and Ramos. The results showed that re-expression of miR-150 reduced proliferation of Daudi and Raji cells. Furthermore, Daudi and Raji, both of which are of EBV-positive germinal center B-cell origin, transduced with miR-150 can be rescued to differentiate toward B-cell terminal stage. However, no significant changes were observed in BJAB or Ramos cells, which are of EBV-negative germinal center B-cell origin. Of note, re-expression of miR-150 also resulted in decreasing c-Myb protein levels. Additionally, c-Myb knockdown in Daudi and Raji cell lines recapitulated the partial characteristics similar to that caused by re-expression of miR-150. Taken together, our findings show that miR-150 can induce EBV-positive BL differentiation by targeting c-Myb.
authors.affiliation: Department of Pathology, Nanfang Hospital affiliated to Southern Medical University, Guangzhou, China.
authors.forename: Shaohong
authors.initials: S
authors.lastname: Chen
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Wang
authors.forename: Xinzhen
authors.initials: X
authors.lastname: Dai
authors.forename: Jianhua
authors.initials: J
authors.lastname: Pan
authors.forename: Juan
authors.initials: J
authors.lastname: Ge
authors.forename: Xiqun
authors.initials: X
authors.lastname: Han
authors.forename: Zijing
authors.initials: Z
authors.lastname: Wu
authors.forename: Xinhua
authors.initials: X
authors.lastname: Zhou
authors.forename: Tong
authors.initials: T
authors.lastname: Zhao
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology / Q000821:virology; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D019169:Jurkat Cells; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics*
chemical_list: D035683:MicroRNAs; D020598:Proto-Oncogene Proteins c-myb; C533097:MIR150, human