Loss of Reelin suppresses cell survival and mobility in non-Hodgkin lymphoma

Dou, Aixia; Wang, Zhilun; Zhang, Ni

doi:10.3892/or.2017.5626

Cited by 12 publications

(10 citation statements)

References 36 publications

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“…Furthermore, Snail silencing successfully attenuated Reelin-induced cisplatin resistance, suggesting that the Snail-orchestrated EMT process may be a vital factor in Reelin-triggered chemoresistance of NSCLC cells. In line with our results, Reelin has been shown to promote mobility in non-Hodgkin lymphoma cells [ 16 ]. In addition, Reelin was also found to suppress the migration of hepatocellular carcinoma cells and mouse embryonic fibroblasts cells [ 32 , 33 ].…”

Section: Discussionsupporting

confidence: 92%

“…Abnormal expression of Reelin promotes tumorigenesis, including the enhancement of cell proliferation, adhesion, and invasion [ 16 , 17 , 25 ]. Previous studies have suggested a correlation between Reelin and tumor chemoresistance [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…Reelin is an extracellular glycoprotein regulating neuronal migration, adhesion, and positioning [ 13 – 15 ]. Although the physiological role of Reelin was considered to be focused in the brain, aberrant expression of Reelin was recently reported in several tumor tissues, including lymphoma [ 16 ], multiple myeloma [ 17 ], esophageal cancer [ 18 ], prostate cancer [ 19 ], and breast cancer [ 20 ]. In addition, increased Reelin expression was proved as a poor prognostic factor in multiple myeloma [ 21 ], high Gleason score prostate cancer [ 19 ], and retinoblastoma [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, increased Reelin expression was proved as a poor prognostic factor in multiple myeloma [ 21 ], high Gleason score prostate cancer [ 19 ], and retinoblastoma [ 22 ]. Moreover, Reelin was shown to promote the pathogenesis of non-Hodgkin lymphoma [ 16 ], multiple myeloma [ 17 ], breast cancer [ 23 ], and mammary tumors [ 24 ]. Notably, further characterization of Reelin revealed its association with drug resistance in multiple myeloma [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

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Reelin Promotes Cisplatin Resistance by Induction of Epithelial-Mesenchymal Transition via p38/GSK3β/Snail Signaling in Non-Small Cell Lung Cancer

Fang

et al. 2020

Med Sci Monit

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Background Emerging evidence suggests the involvement of Reelin in chemoresistance in various cancers. However, its function in cisplatin (DDP) sensitivity of non-small cell lung cancer (NSCLC) needs to be investigated. Material/Methods Reelin expression in cisplatin-sensitive A549 cells and cisplatin-resistant NSCLC (A549/DDP) cells was analyzed by western blot analysis. qRT-PCR, western blotting, immunofluorescence, CCK-8 assays, Annexin V/propidium iodide apoptosis assay, and Transwell migration assays were carried out to determine the function of Reelin on DDP resistance. Results Reelin was markedly increased in A549/DDP cells relative to A549 cells. Knockdown of Reelin enhanced DDP chemosensitivity of A549/DDP cells, whereas overexpression of Reelin enhanced DDP resistance of A549, H1299, and H460 cells. Reelin induced DDP resistance in NSCLC cells via facilitating epithelial-mesenchymal transition (EMT). Furthermore, Reelin modulated p38/GSK3β signal transduction and promoted Snail (EMT-associated transcription factor) expression. Suppression of p38/Snail reversed Reelin-induced EMT and resistance of NSCLC cells to DDP. Conclusions These data indicated that Reelin induces DDP resistance of NSCLC by regulation of the p38/GSK3β/Snail/EMT signaling pathway and provide evidence that Reelin suppression can be an effective strategy to suppress DDP resistance in NSCLC.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Reelin Promotes Cisplatin Resistance by Induction of Epithelial-Mesenchymal Transition via p38/GSK3β/Snail Signaling in Non-Small Cell Lung Cancer

Fang

et al. 2020

Med Sci Monit

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“…Ad-p53 therapy resulted in a decrease in the immune suppressive chemokines CCL18 by >27-fold and CCL14 by >25-fold. CD209 (DC-SIGN), MARCO and RELN genes function in the down regulation of the immune system through IL10 and inhibitory tumor associated macrophage mechanisms respectively (22)(23)(24). CD209 is down-regulated by >20-fold, MARCO is down-regulated by >18-fold and RELN by > 17 fold.…”

Section: Gene Expression Profiles Induced By Ad-p53 Treatmentmentioning

confidence: 99%

Tumor Suppressor Immune Gene Therapy to Reverse Immunotherapy Resistance

Chada¹,

Wiederhold²,

Menander³

et al. 2021

Preprint

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BackgroundWhile immune checkpoint inhibitors are becoming a standard of care for multiple types of cancer, the majority of patients do not respond to this form of immunotherapy. New approaches are required overcome resistance to immunotherapies.MethodsWe investigated the effects of adenoviral p53 (Ad-p53) gene therapy in combination with immune checkpoint inhibitors and selective IL2 or IL15 CD122/132 agonists in the aggressive B16F10 tumor model resistant to immunotherapies. To assess potential mechanisms action, pre and post Ad-p53 treatment biopsies were evaluated for changes in gene expression profiles by Nanostring IO 360 assays.ResultsSubstantial synergy of “triplet” Ad-p53 + CD122/132 + anti-PD-1 therapy resulted in potential curative effects associated with complete tumor remissions of both primary and contralateral tumors. Interestingly, contralateral tumors which were not injected with Ad-p53 showed robust abscopal effects resulting in statistically significant decreases in tumor size and increased survival (p<0.001). None of the monotherapies or doublet treatments induced complete tumor regressions. Ad-p53 treatment increased Type I Interferon, CD8+ T cell, immuno-proteosome antigen presentation and tumor inflammation gene signatures. Ad-p53 treatment also decreased immune suppressive TGF-beta, beta-catenin, macrophage, and endothelium gene signatures, which may contribute to enhanced immune checkpoint inhibitor (CPI) efficacy. Unexpectedly, a number of previously unidentified, strongly p53 down regulated genes associated with stromal pathways and IL10 expression identified novel anti-cancer therapeutic applications.ConclusionsThese results imply the ability of Ad-p53 to induce efficacious local and systemic anti-tumor immune responses with the potential to reverse resistance to immune checkpoint inhibitor therapy when combined with CD122/132 agonists and immune checkpoint blockade. Our findings further imply that Ad-p53 has multiple complimentary immune mechanisms of action which support future clinical evaluation of triplet Ad-p53, CD122/132 agonist and immune checkpoint inhibitor combination treatment.

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The depletion of Circ‐PRKDC enhances autophagy and apoptosis in T‐cell acute lymphoblastic leukemia via microRNA‐653‐5p/Reelin mediation of the PI3K/AKT/mTOR signaling pathway

Zhang

Fang

et al. 2021

The Kaohsiung J of Med Scie

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A range of circular (Circ) RNAs have been demonstrated to be of therapeutic significance for the treatment of acute lymphoblastic leukemia (ALL). Here, we investigated the mechanisms underlying the action of Circ-PRKDC and the microRNA-653-5p/ Reelin (miR-653-5p/RELN) axis in T-cell ALL (T-ALL).Clinical specimens were obtained from patients with T-ALL (n = 39) and healthy controls (n = 30). In each specimen, we determined the expression levels of Circ-PRKDC, miR-653-5p, and RELN. Human T-ALL cells (Jurkat) were transfected with Circ-PRKDC-or miR-653-5p-related sequences to investigate cell proliferation, apoptosis, and autophagy. We also determined the levels of Circ-PRKDC, miR-653-5p, RELN, and signaling proteins related to phosphoinositide 3-kinase (PI3K), AKT, and mammalian target of rapamycin (mTOR). Finally, we decoded the interactions between Circ-PRKDC, miR-653-5p, and RELN. The expression levels of Circ-PRKDC and RELN were upregulated in T-ALL tissues and cells while the levels of miR-653-5p were downregulated. Thereafter, then silencing of Circ-PRKDC, or the enforced expression of miR-653-5p, repressed the expression of RELN and the activation of the PI3K/AKT/mTOR signaling pathway, thus enhancing cell autophagy and apoptosis, and disrupting cell proliferation. Circ-PRKDC acted a sponge for miR-653-5p while miR-653-5p targeted RELN. The knockdown of miR-653-5p abrogated the silencing of Circ-PRKDCinduced effects in T-ALL cells. The depletion of Circ-PRKDC elevated miR-653-5p to silence RELN-mediated PI3K/AKT/mTOR signaling activation, thereby enhancing autophagy and apoptosis in T-ALL cells.

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Loss of Reelin suppresses cell survival and mobility in non-Hodgkin lymphoma

Cited by 12 publications

References 36 publications

Reelin Promotes Cisplatin Resistance by Induction of Epithelial-Mesenchymal Transition via p38/GSK3β/Snail Signaling in Non-Small Cell Lung Cancer

Reelin Promotes Cisplatin Resistance by Induction of Epithelial-Mesenchymal Transition via p38/GSK3β/Snail Signaling in Non-Small Cell Lung Cancer

Tumor Suppressor Immune Gene Therapy to Reverse Immunotherapy Resistance

The depletion of Circ‐PRKDC enhances autophagy and apoptosis in T‐cell acute lymphoblastic leukemia via microRNA‐653‐5p/Reelin mediation of the PI3K/AKT/mTOR signaling pathway

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