Effects of microRNA-21 on apoptosis by regulating the expression of PTEN in diffuse large B-cell lymphoma

Abstract

Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy and the most common subtype of non-Hodgkin lymphoma in China. However, many cases still remain biologically and clinically heterogeneous, indicating that the DLBCL mechanism remains unclear. MicroRNAs (miRNAs) are critically responsible for lymphomagenesis. We found that plasma miR-21 level was significantly higher in B-cell lymphoma. However, the exact contribution of miR-21 in DLBCL remains unknown.To determine the function and mechanism of miR-21 in DLBCL, miR-21 and phosphatase and tensin homolog (PTEN) expressions were examined through real-time PCR and immunohistochemical methods. Moreover, the effects of antisense oligonucleotide (ASO) targeting miR-21 (ASO-21) were observed in DLCBL cell line.MiR-21 expressions in cell line and tissues of patients were significantly higher than those in normal controls, which were inversely correlated with PTEN expression. MiR-21 expression was significantly higher in stage III/IV patients than in stage I/II patients. PTEN protein was expressed positively in only 6 patients with DLBCL (6/26). MiR-21 expression level in the PTEN-negative group was 11.73 (2.13–64.29), which was significantly higher than that in the PTEN-positive group (1.04, 0.67–15.15; P = .038). After down-regulating the miR-21 expression, apoptosis of DLBCL cells increased and PTEN protein was up-regulated in ASO-21-treated cells compared with SCO-21-treated cells by western blot.These results suggested that miR-21 affects apoptosis of lymphoma cells by regulating the expression of PTEN in DLBCL, which may be associated with increased poor prognosis for DLBCL patients and represents a useful approach for DLBCL treatment.

Systematic Review of the Potential of MicroRNAs in Diffuse Large B Cell Lymphoma

“…Twenty-one studies analyzed the expression of miRNAs by comparing DLBCL cases vs healthy controls [17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37]. These 21 studies provided a total of 140 differentially expressed microRNAs in DLBCL patients compared with healthy control individuals as shown in Table S1.…”

High-Throughput MicroRNA Profiling of Vitreoretinal Lymphoma: Vitreous and Serum MicroRNA Profiles Distinct from Uveitis

“…Previous studies have investigated miRNA profiles in diffuse large B-cell lymphoma (DLBCL) [41][42][43][44][45][46]. miR-181a-5p is reported to be upregulated in peripheral blood of acute lymphoblastic leukemia compared with normal peripheral blood mononuclear cells [47].…”

HMGA Proteins in Hematological Malignancies

“…This is a proteasome inhibitor used to suppress Diffuse large B-cell lymphoma (DLBCL) progression [ 223 , 224 , 225 ]. DLBCL is the most frequent non-Hodgkin lymphoma, showing variable clinical presentations as well as variable therapy responses [ 226 , 227 , 228 ]. In vitro studies on DLBCL CRL-2630 cells showed that BTZ treatment significantly inhibited the proliferation of DLBCL CRL-2630 cells [ 229 ].…”