Aberrant Overexpression and Regulatory Mechanism of Mir-21 in Diffuse Large B Cell Lymphoma

MicroRNAs (miRNAs) are critically responsible for lymphomagenesis. We found that miR-21 expression was significantly higher in diffuse large B cell lymphoma (DLBCL) line and paraffin-embedded tissue of primary lymphoma (n = 26) than that in normal lymph nodes (n = 10). To determine the functions of miR-21 in lymphomagenesis, we examined phosphatase and tensin homolog (PTEN) expression using immunohistochemical SP method in specimens of primary DLBCL. MiR-21 expression is negatively correlated with PTEN expression, but positively correlated with LDH. MiR-21 expression was significantly higher in stage III / IV patients than in stage I/II patients. Moreover, we examined the effects of antisense oligonucleotide (ASO) targeting miR-21 (ASO-21) in the DLCBL line overexpressing this miRNA. Electroporation was used to transfect ASO-21 into the cells, which showed slight endogenous miR-21 expression. Downregulating miR-21 expression resulted in increased incidence of apoptosis and PTEN upregulation. These results provide relevant new insight into the pathogenesis of DLBCL and suggest that targeting miR-21 may represent a useful approach for DLBCL treatment, and that high levels of miR-21 may be associated with increased poor prognosis for DLBCL patients.