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Background MicroRNAs (miRNAs) are a class of small RNAs that function as negative gene regulators through binding to complementary sequences in the 3 UTR of target mRNA.MicroRNA-21(miR-21) has been suggested over-expressed in a wide range of cancers.The aim of this study was to investigate the expression and role of miR-21 in regulation of cell biological behavior in diffuse large B-cell lymphoma (DLBCL).Methods MiR-21 expression was investigated in three DLBCL cell lines and normal B-cell, by real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR).To determine the possible role of miR-21 in the biological behavioral properties of DLBCL, we used miR-21 knockdown, which was carried out according to transfect with anti-miR-21 or miR-control.In addition, PDCD4 and PTEN were studied by luciferase report assay, qPR-PCR and western blotting.Results The results showed that miR-21 was up-regulated significantly in activated B-cell (ABC)-like DLBCL cells compared to germinal centre (GC)-like DLBCL cells.Inhibition of miR-21 induced suppression of the proliferation and invasion, and increasing of apoptosis in DLBCL.Meanwhile, knockdown of miR-21 increased the expression of PDCD4 and PTEN at protein level but not at mRNA level, and the relative luciferase activity of the reporter containing wild-type 3 UTR of PDCD4 and PTEN were apparently suppressed.Conclusions MiR-21 regulates multiple programs like proliferation,invasion and apoptosis, so it may provide potential therapeutic applications in DLBCL.