MiRNAs are Unlikely to be Involved in Retinoid Receptor Gene Regulation in Pancreatic Cancer Cells

Yin, Shuai; Bleul, Tim; Zhu, Yifan; Isayev, Orkhan; Werner, Jens; Bazhin, Alexandr V.

doi:10.1159/000485276

Cited by 9 publications

(5 citation statements)

References 39 publications

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“…The expression of retinoid receptors in cancers can be altered by different mechanisms including 1) mutation or deletion of the gene, 2) transcriptional repression or 3) post-transcriptional repression [44]. We were interested in RAR␣ regulation at the post-transcriptional level by miRs, resulting in either destabilization of the target mRNA or translational repression [45].…”

Section: Discussionmentioning

confidence: 99%

Impact of RARα and miR-138 on retinoblastoma etoposide resistance

Busch

Miroschnikov

Dankert

et al. 2021

TUB

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BACKGROUND: Retinoblastoma (RB) is the most common childhood eye cancer. Chemotherapeutic drugs such as etoposide used in RB treatment often cause massive side effects and acquired drug resistances. Dysregulated genes and miRNAs have a large impact on cancer progression and development of chemotherapy resistances. OBJECTIVE: This study was designed to investigate the involvement of retinoic acid receptor alpha (RARα) in RB progression and chemoresistance as well as the impact of miR-138, a potential RARα regulating miRNA. METHODS: RARα and miR-138 expression in etoposide resistant RB cell lines and chemotherapy treated patient tumors compared to non-treated tumors was revealed by Real-Time PCR. Overexpression approaches were performed to analyze the effects of RARα on RB cell viability, apoptosis, proliferation and tumorigenesis. Besides, we addressed the effect of miR-138 overexpression on RB cell chemotherapy resistance. RESULTS: A binding between miR-138 and RARα was shown by dual luciferase reporter gene assay. The study presented revealed that RARα is downregulated in etoposide resistant RB cells, while miR-138 is endogenously upregulated. Opposing RARα and miR-138 expression levels were detectable in chemotherapy pre-treated compared to non-treated RB tumor specimen. Overexpression of RARα increases apoptosis levels and reduces tumor cell growth of aggressive etoposide resistant RB cells in vitro and in vivo. Overexpression of miR-138 in chemo-sensitive RB cell lines partly enhances cell viability after etoposide treatment. CONCLUSIONS: Our findings show that RARα acts as a tumor suppressor in retinoblastoma and is downregulated upon etoposide resistance in RB cells. Thus, RARα may contribute to the development and progression of RB chemo-resistance.

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Section: Discussionmentioning

confidence: 99%

Impact of RARα and miR-138 on retinoblastoma etoposide resistance

Busch

Miroschnikov

Dankert

et al. 2021

TUB

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“…Protein concentration was assessed with the BCA method. Western blot analysis was carried out as described previously 10 . After blocking with 5% ( w / v ) of milk in TBST, the PVDF membranes were incubated overnight with an antibody against the protein of interest (Anti-mouse HMGB1, phospho-p65, phospho-p38 and GAPDH), followed with incubation with secondary antibodies for 1 h at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Experimental postoperative ileus: is Th2 immune response involved?

Lin¹,

Kühn²,

Schiergens³

et al. 2021

Int. J. Med. Sci.

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Rationale: Postoperative ileus (POI) is a frequent complication arising after gastrointestinal surgery but pathogenesis of POI is still not fully understood. While Th1 immune cells are implicated in POI, the involvement of Th2 cells has not yet been clarified. Given the impact of reactive oxygen species (ROS) in the regulation of Th1 and Th2 balance, we hypothesized that not only Th1 but also Th2 immune response can be involved in the development of experimental POI. Methods: The intestinal transit test was performed using carbon gum arabic. Electron microscopy was employed to assess tissue morphology and the presence of immune cells. Cytokines, IgE and ROS were measured. Immune cells from Peyer's patches were analyzed by Flow Cytometry and toluidine blue staining was used for detection of mast cells. Transcriptional factors were analyzed by Western blot. Results: POI is associated with an increase in both Th2 cytokines and Th2 cells. We have further demonstrated that POI induces a Th2-dependent activation of memory and non-memory B cells. This was accompanied by an increase in a number of mast cells in the colon of POI mice as well by an increased IgE and histamine plasma levels. We found that POI-induced accumulation of ROS was associated with an increased expression of the transcriptional factors HMBGI, NF-κB, and p38. This increased expression seemed to be associated with a Th2 response. Conclusion: Th2 immune response can be involved in the activation of mast cells in POI, which was associated with ROS mediated activation of NF-κB and p38 MAPK signaling pathway.

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“…Classically, after RNA-induced silencing complex (RISC) loading, mature miRNA directs the complex to target mRNAs, leading to expressive suppression. Many target genes of tumor-associated miRNAs have been found to regulate cancer development pathways [12][13][14][15]. Hence, emerging studies have discovered that the differential expression of miRNA, such as miR-21, miR-99a, and miR-34a, could predict the prognosis of PaCa patients [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Integrating MicroRNA Expression Profiling Studies to Systematically Evaluate the Diagnostic Value of MicroRNAs in Pancreatic Cancer and Validate Their Prognostic Significance with the Cancer Genome Atlas Data

Zhang

Pan

et al. 2018

Cell Physiol Biochem

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Background/Aims: MicroRNAs (miRNAs) are promising biomarkers for pancreatic cancer (PaCa). However, systemic and unified evaluations of the diagnostic value of miRNAs are lacking. Therefore, we performed a systematic evaluation based on miRNA expression profiling studies. Methods: We obtained miRNA expression profiling studies from Gene Expression Omnibus (GEO) and ArrayExpress (AE) databases and calculated the pooled sensitivity, specificity, and summary area under a receiver operating characteristic (ROC) curve for every miRNA. According to the area under the curve (AUC), we identified the miRNAs with diagnostic potentiality and validated their prognostic role in The Cancer Genome Atlas (TCGA) data. Gene Ontology (GO) annotations and pathway enrichments of the target genes of the miRNAs were evaluated using bioinformatics tools. Results: Ten miRNA expression profiling studies including 958 patients were used in this diagnostic meta-analysis. A total of 693 miRNAs were measured in more than 9 studies. The top 50 miRNAs with high predictive values for PaCa were identified. Among them, miR-130b had the best predictive value for PaCa (pooled sensitivity: 0.73 [95% confidence intervals (CI) 0.44-0.91], specificity: 0.81 [95% CI 0.59–0.93], and AUC: 0.84 [95% CI 0.73–0.95]). We identified nine miRNAs (miR-23a, miR-30a, miR-125a, miR-129-1, miR-181b-1, miR-203, miR-221, miR-222, and miR-1301) associated with overall survival in PaCa patients by combining our results with TCGA data. The results of a Cox model revealed that two miRNAs (miR-30a [hazard ratio (HR)=2.43, 95% CI 1.05-5.59; p=0.037] and miR-203 [HR=3.14, 95% CI 1.28-7.71; p=0.012]) were independent risk factors for prognosis in PaCa patients. In total, 405 target genes of the nine miRNAs were enriched with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and cancer-associated pathways such as Ras signaling pathways, phospholipase D signaling pathway, and AMP-activated protein kinase (AMPK) signaling pathway were revealed among the top 20 enriched pathways. There were significant negative correlations between miR-181b-1 and miR-125a expression levels and the methylation status of their promoter region. Conclusion: Our study performed a systematic evaluation of the diagnostic value of miRNAs based on miRNA expression profiling studies. We identified that miR-23a, miR-30a, miR-125a, miR-129-1, miR-181b-1, miR-203, miR-221, miR-222, and miR-1301 had moderate diagnostic value for PaCa and predicted overall survival in PaCa patients.

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MiRNAs are Unlikely to be Involved in Retinoid Receptor Gene Regulation in Pancreatic Cancer Cells

Cited by 9 publications

References 39 publications

Impact of RARα and miR-138 on retinoblastoma etoposide resistance

Impact of RARα and miR-138 on retinoblastoma etoposide resistance

Experimental postoperative ileus: is Th2 immune response involved?

Integrating MicroRNA Expression Profiling Studies to Systematically Evaluate the Diagnostic Value of MicroRNAs in Pancreatic Cancer and Validate Their Prognostic Significance with the Cancer Genome Atlas Data

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