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

Liu,Ke; Du,Jingxia; Ruan,Linhai

doi:10.3892/etm.2017.5021

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

Authors:
- Ke Liu
- Jingxia Du
- Linhai Ruan
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Affiliations: Department of Hematology, The First Affiliated Hospital and College of Clinical Medicine, Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China, Department of Pharmacology, Medical College, Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China
Published online on: August 24, 2017 https://doi.org/10.3892/etm.2017.5021
Pages: 4489-4496

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Abstract

Diffuse large B‑cell lymphoma (DLBCL), one of the most frequently diagnosed non‑Hodgkin lymphoma (NHL), is partly attributed to hereditary factors. MicroRNA‑21 (miR‑21) 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.

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