Role of micro RNA in the pathogenesis of malignant lymphoma

Micro RNA (mi RNA ) are non‐coding regulatory RNA usually consisting of 20−24 nucleotides. Over the past decade, increases and decreases in mi RNA expression have been shown to associate with various types of disease, including cancer. The first two known mi RNA aberrations resulted from altered expression of DLEU2 and C13orf25 in hematological malignancies. DLEU2 , which encodes miR‐15a and miR‐16‐1, was discovered from 13q14 deletion in chronic lymphocytic leukemia, while C13orf25 , which encodes six mature mi RNA (miR‐17, miR‐18, miR‐19a, miR‐19b, miR‐20a and miR‐92a), was identified from 13q31 amplification in aggressive B‐cell lymphomas. These mi RNA were downregulated or upregulated in accordance with genomic deletion or amplification, which suggests that they contribute to tumorigenesis through altered regulation of target oncogenes or tumor suppressors. Consistent with that idea, miR‐15a/16‐1 is known to regulate Bcl2 in chronic lymphocytic leukemia, and miR‐17‐92 regulates the tumor suppressors p21, Pten and Bim in aggressive B‐cell lymphomas. Dysregulation of other mi RNA , including miR‐21, miR‐29, miR‐150 and miR‐155, have also been shown to play crucial roles in the pathogenesis of aggressive transformed, high‐grade and refractory lymphomas. Addition of mi RNA dysregulation to the original genetic events likely enhances tumorigenicity of malignant lymphoma through activation of one or more signaling pathways.