MicroRNA-21 regulates the sensitivity of diffuse large B-cell lymphoma cells to the CHOP chemotherapy regimen

Bai, Hao; Wang, Ju; Deng, Chao; Yang, Xiaoyu; Wang, Chun; Xu, Rang

doi:10.1007/s12185-012-1256-x

Cited by 59 publications

(59 citation statements)

References 37 publications

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“…PD-1 binds to 2 ligands, PD-L1 and PD-L2, belonging to the B7 family (6). PD-L1 is expressed in DLBCL cells, including CRL2631 (9,11). To examine the role of PD-1/PD-L1 axis in CHOP-induced CRL2631 injury, the expression of PD-L1 was knocked down by introducing the validated siRNA that specifically targets to human PD-L1 (14).…”

Section: Pd-1/pd-l1 Interaction Decreases the Cytotoxic Effects Of Chmentioning

confidence: 99%

Over-activated PD-1/PD-L1 axis facilitates the chemoresistance of diffuse large B-cell lymphoma cells to the CHOP regimen

et al. 2017

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Abstract.Interaction between the programmed cell death ligand 1 (PD-L1) and programmed cell death 1 (PD-1) contributes to tumor cell resistance to chemotherapeutic agents. PD-L1 is expressed in the cells of diffuse large B-cell lymphoma (DLBCL), one common type of malignant non-Hodgkin lymphomas. However, little is known about how the PD-1/PD-L1 pathway functions in the pathogenesis of DLBCL. Therefore, the present study investigated whether and how the PD-1/PD-L1 axis is involved in regulating the sensitivity of CRL2631, a DLBCL cell line, to the CHOP (Cyclophosphamide, Hydroxydaunorubicin/adriamycin, Oncovin/vincristine and Prednisone) chemotherapeutic regimen. CHOP treatment significantly decreased cell survival rate and increased apoptosis in CRL2631 cells. The application of recombinant human PD-1 (rPD-1) significantly decreased the cytotoxic effects of the CHOP regimen in CRL2631 cells, but not in the CRL2631 cells with PD-L1 deficiency. In the CRL2631 cells, rPD-1 enhanced the activity of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt1) pathway. However, the activity level of the PI3K/Akt1 pathway was decreased in CHOP-treated CRL2631 cells. The selective PI3K inhibitor BKM120 significantly increased CHOP-induced apoptosis, but this effect was abolished by rPD-1 and aggravated by PD-L1 knockdown. In CHOP-treated PD-L1 knockdown cells, the increased apoptosis was markedly inhibited by the overexpression of constitutively active Akt1. Overall, the results demonstrate that the over-activated PD-1/PD-L1 axis is associated with chemotherapeutic resistance of DLBCL cells to the CHOP regimen, potentially through a PI3K-dependent mechanism.

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Section: Pd-1/pd-l1 Interaction Decreases the Cytotoxic Effects Of Chmentioning

confidence: 99%

Over-activated PD-1/PD-L1 axis facilitates the chemoresistance of diffuse large B-cell lymphoma cells to the CHOP regimen

et al. 2017

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“…Furthermore, overexpression of miR-21, miR-155 and miR-17-92 may be observed in lymphomas derived from B cells, T cells or natural killer cells (8,11,12). Notably, miR-21 has a vital role in regulating the chemosensitivity of DLBCL cells (13) and Bcl-2, a tumor-associated and anti-apoptotic molecule, has a key role in the chemoresistance of NHL and has been considered as a prognostic biomarker for DLBCL (14). However, the role of miR-21 in regulating the expression of Bcl-2 in DLBCL remains unclear, and there are no in-depth studies on the relationship between miR-21 and Bcl-2 in DLBCL.…”

Section: Introductionmentioning

confidence: 99%

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

Liu

Ruan

2017

Exp Ther Med

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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. 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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“…It was recently suggested that miR-21 might modulate the PI3K/AKT pathway by targeting PTEN upstream and FOXO1 downstream [11]. In addition, miRNA-21 expression was correlated with chemoresistance in DLBCL cells through the up-regulation of multi-drug resistance (MDR1) expression and activity which is mediated by suppression of PTEN and activation of AKT pathway [12].…”

Section: Introductionmentioning

confidence: 99%

The Diagnostic and Prognostic Impact of Serum miRNA-21 in a Sample of Hepatitis C/None Hepatitis Diffuse Large B Cell Lymphoma Egyptian Patients

Elhalawani¹,

Nazir²,

Mashali³

et al. 2017

AJMB

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Background: Circulating microRNAs are potential biomarkers of diagnostic and prognostic impact in various inflammatory and malignant diseases. Aim: Linking inflammation with malignancy, we studied miRNA-21 in sera of hepatitis-C-virus (HCV) and none hepatitis diffuse large B-cell lymphoma (DLBCL) patients, aiming to identify its differential expression and prognosis in DLBCL with its subtypes; germinal center B-cell (GCB) and activated B-cell-like (ABC) and to evaluate its relation with HCV. Subjects and Methods: MiRNA-21 expression was measured using TaqMan quantitative RT-PCR in sera of 30 newly diagnosed DLBCL patients (HCV positive (n = 10), HCV negative (n = 20)) and 20 controls (HCV positive (n = 10), HCV negative (n = 10)). Results: MiRNA-21 expression was significantly higher in DLBCL patients than in control (p = 0.00). Significant positive correlations between miRNA-21 and LDH, IPI and disease stage were detected (p < 0.05). Significantly higher miRNA-21 was detected in ABC sub-type compared to GCB sub-type (p = 0.00). Higher miRNA-21 was associated with worse response (p = 0.016), 2 years overall (p = 0.017) and progression free survival with statistical significance (p= 0.003). Significantly higher miRNA-21 levels were detected in HCV positive DLBCL patients compared to HCV negative patients (p = 0.00). Higher miRNA-21 levels were detected in HCV positive ABC subtype than GCB subtype (p = 0.05). Significantly higher levels were also detected in HCV positive controls compared to HCV negative controls. Conclusion: Our study shows that miRNA-21 is over expressed in our patients with DLBCL, displaying higher levels in ABC than in GCB subtypes. MiR-NA-21 is associated with poor response to treatment and survival in DLBCL. MiR-NA-21 is a potential marker of necro-inflammation independent of its role in tumorogenesis, showing higher expression in HCV positive DLBCL patients compared to none hepatitis patients.

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MicroRNA-21 regulates the sensitivity of diffuse large B-cell lymphoma cells to the CHOP chemotherapy regimen

Cited by 59 publications

References 37 publications

Over-activated PD-1/PD-L1 axis facilitates the chemoresistance of diffuse large B-cell lymphoma cells to the CHOP regimen

Over-activated PD-1/PD-L1 axis facilitates the chemoresistance of diffuse large B-cell lymphoma cells to the CHOP regimen

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

The Diagnostic and Prognostic Impact of Serum miRNA-21 in a Sample of Hepatitis C/None Hepatitis Diffuse Large B Cell Lymphoma Egyptian Patients

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