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. B urkitt lymphoma is a highly aggressive B-cell malignancy, identified and described for the first time by Dennis Burkitt in 1958.(1) According to the EBV infection status, BLs are divided into two subgroups, EBV-positive and EBV-negative.(2) Burkitt lymphomas have a tendency to morphologically resemble germinal center (GC) cells, (3) and to immunophenotypically express characteristic GC cell markers such as CD10 and BCL6, and coexpress B-cell markers CD19 and CD20, (4) which suggests follicle center B-cell origin for this lymphoma. In recent years, efforts have focused on improving therapy for this, the fastest growing human tumor, while minimizing treatment-associated toxicity. Outcome with intensive chemotherapy has improved and is now excellent in children, but the prognosis is poor in elderly adults. In addition, there are significant associated toxicities, such as frequent myelosuppression, mucositis, neuropathy, and complication of tumor lysis syndrome.(5,6) Therefore, it is imperative and important to pursuit more effective therapies.MicroRNAs, a novel class of small non-coding RNAs of approximately 19-26 nt, exert multiple cellular functions and play critical roles in cellular proliferation, apoptosis, cellular differentiation, and tumorigenesis.(7-9) MicroRNA expression profiling studies have found that in hematopoiesis, certain miRNAs are expressed in a stage-specific fashion in the lymphoid hematopoietic system.(10-14) Therefore, deregulations of their expression may result in the development of hematopoietic malignancies. (15) MicroRNA-150 has attracted our great attention in hematopoiesis among a large number of miRNAs in recent years, which has been studied in B, T, and NK ⁄ T cells. (16)(17)(18)(19)(20) There is strong evidence that miR-150 is preferentially expressed in mature lymphocytes, but not their progenitors. Ectopic miR-150 expression of murine hematopoietic stem cells impairs the transition of pro-B to pre...

Mda-7/IL-24 enhances sensitivity of B cell lymphoma to chemotherapy drugs

“…B cell lymphoma is one of the most common types of hematopoietic tumors (16). Chemotherapy is the first-line choice for lymphoma treatment.…”

Reversal of microRNA-150 silencing disadvantages crizotinib-resistant NPM-ALK(+) cell growth

“…Altogether, our findings suggest that miR-150 overexpression leads to a drastic inhibition of cell growth and tumor formation through repression of the downstream target MYB, a master regulator of proliferation (Figure 8; refs. [58][59][60]. Indeed, it is a known fact that, in NPM-ALK(+) ALCL cells, the functional effects of MYB are modulated by transcription factors and cell cycle proteins, which include MYC and cyclin-D1 (60)(61)(62).…”

MIR150 (microRNA 150)

“…MIR150 is dramatically down-regulated in BL patients; MYB and Survivin (BIRC5) are the targetrs of MIR150 (Wang et al, 2014). In addition, MIR150 can induce Epstein Barr virus-positive BL differentiation by targeting MYB (Chen et al, 2013).…”