MicroRNA‑21 regulates the viability and apoptosis of diffuse large B‑cell lymphoma cells by upregulating B cell lymphoma‑2

Abstract

Abstract. Diffuse large B-cell lymphoma (DLBCL), one of the most frequently diagnosed non-Hodgkin lymphoma (NHL), is partly attributed to hereditary factors. is an oncogenic substance that induces NHL and primarily targets tumor-suppressive molecules, such as B cell lymphoma-2 (Bcl-2). The present study explored whether Bcl-2, targeted by miR-21, would affect the development of NHL. Specimens were harvested from 55 patients with DLBCL who had undergone surgical treatment. Expression levels of miR-21 and Bcl-2 were evaluated through reverse transcription-quantitative polymerase chain reaction, immunohistochemistry and western blotting. Luciferase-reporter assays were performed to investigate the potential association between miR-21 and Bcl-2. MTT assays, flow cytometric analysis and caspase-3 activity assays were used to evaluate cell viability and apoptosis of DLBCL cells, respectively. Furthermore, statistical analysis was conducted using SPSS 19.0 software and the expression levels of miR-21 and Bcl-2 within DLBCL tissues were significantly upregulated when compared to those in normal tissues (P<0.01). As predicted by TargetScan, perfect base pairing was observed between the seed sequence of mature miR-21 and the 3' untranslated region of Bcl-2 mRNA. Dual luciferase reporter gene assays also revealed that miR-21 significantly facilitated the luciferase activity of Bcl-2 wild-type, with 61% upregulation (P<0.01) observed. MTT assays demonstrated that the viability of OCI-LY3 cells was decreased when cells were transfected with miR-21 inhibitor or Bcl-2 small interfering RNA and compared with those of control and negative control groups (all P<0.05). The apoptosis rate and caspase-3 activity level of the miR-21 group were 2.73±0.48 and 0.47±0.05, respectively, which were both significantly different from the groups with lower levels of miR-21 expression levels (all P<0.01). Since miR-21 may contribute to increased viability and decreased apoptosis of DLBCL cells through targeting Bcl-2, both Bcl-2 and miR-21 are likely to serve as effective targets for developing novel DLBCL treatments in the future.

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.…”

“…Regarding the miRNAs that were concordantly deregulated in more than two studies, we identified two miRNAs that were repeatedly reported to be up-regulated in DLBCL patients (miR-155-5p [17,22,24,26,28,30,32,33,34], miR-21-5p [19,22,26,28,33,36], although some studies did not find a significant association (miR-155-5p [27,29], miR-21-5p [27,32]).We also identified two miRNAs with contradictory results. On the one hand, miR-150-5p was found to be down-regulated in DLBCL patients in four studies [18,28,31,32] and contradictorily up-regulated in DLBCL patients in another study [29], while no significant association was reported in the remaining study [27].…”

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].…”

“…According to the canonical miRNA-mRNA interaction, upregulation of these posttranscriptional elements in VRL may promote downregulation of important genes responsible for B-cell lymphoma. In fact, 21-5p has been associated with survival and proliferation of malignant cells in DLBCL [43,72].…”

The Role of Noncoding RNAs in B-Cell Lymphoma

“…In diffuse large B-cell lymphoma (DLBCL), the most common invasive NHL, more than 100 miRNAs have been reported to be deregulated (40,41,89,90), including numerous miRNAs with identified biological functions, such as miR-15a/16, miR-21, miR-34a, miR-106, miR-146a/b, miR-150, and miR-155 (91)(92)(93)(94)(95)(96)(97)(98). A study reported 2,632 novel lncRNAs specifically expressed in DLBCL clinical samples compared with normal B cells, nearly half of which were differentially expressed and clustered across different groups of DLBCL samples (99), suggesting that these lncRNAs may participate in DLBCL pathogenesis.…”