Genome-wide mRNA and miRNA expression data analysis to screen for markers involved in sarcomagenesis in human chondrosarcoma cell lines

Abstract BACKGROUND Different technologies, such as quantitative real-time PCR or microarrays, have been developed to measure microRNA (miRNA) expression levels. Quantification of miRNA transcripts implicates data normalization using endogenous and exogenous reference genes for data correction. However, there is no consensus about an optimal normalization strategy. The choice of a reference gene remains problematic and can have a serious impact on the actual available transcript levels and, consequently, on the biological interpretation of data. CONTENT In this review article we discuss the reliability of the use of small RNAs, commonly reported in the literature as miRNA expression normalizers, and compare different strategies used for data normalization. SUMMARY A workflow strategy is proposed for normalization of miRNA expression data in an attempt to provide a basis for the establishment of a global standard procedure that will allow comparison across studies.

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Integration of genome-wide mRNA and miRNA expression, and DNA methylation data of three cell lines exposed to ten carbon nanomaterials

Data in Brief ◽

10.1016/j.dib.2018.05.107 ◽

2018 ◽

Vol 19 ◽

pp. 1046-1057 ◽

Cited By ~ 2

Author(s):

Giovanni Scala ◽

Veer Marwah ◽

Pia Kinaret ◽

Jukka Sund ◽

Vittorio Fortino ◽

...

Keyword(s):

Dna Methylation ◽

Cell Lines ◽

Mirna Expression ◽

Carbon Nanomaterials ◽

Methylation Data ◽

Genome Wide

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Decision tree‑based classifiers for lung cancer diagnosis and subtyping using TCGA miRNA expression data

Oncology Letters ◽

10.3892/ol.2019.10462 ◽

2019 ◽

Cited By ~ 3

Author(s):

Masih Sherafatian ◽

Fateme Arjmand

Keyword(s):

Lung Cancer ◽

Decision Tree ◽

Cancer Diagnosis ◽

Mirna Expression ◽

Expression Data ◽

Lung Cancer Diagnosis ◽

Mirna Expression Data

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miRNA Expression Analysis: Cell Lines HCC1500 and HCC1937 as Models for Breast Cancer in Young Women and the miR-23a as a Poor Prognostic Biomarker

Breast Cancer Basic and Clinical Research ◽

10.1177/1178223420977845 ◽

2020 ◽

Vol 14 ◽

pp. 117822342097784

Author(s):

Sara S Oltra ◽

Maria Peña-Chilet ◽

Maria T Martinez ◽

Eduardo Tormo ◽

Juan Miguel Cejalvo ◽

...

Keyword(s):

Breast Cancer ◽

Cell Lines ◽

Young Women ◽

Mirna Expression ◽

Young Patients ◽

Breast Cancer Patients ◽

Old Patients ◽

Cellular Models ◽

Hcc1937 Cell ◽

Mirna Expression Data

Purpose: The study of breast cancer nearly always involves patients close to menopause or older. Therefore, young patients are mostly underrepresented. Our aim in this study was to demonstrate biological differences in breast cancer of young people using as a model available cell lines derived from people with breast cancer younger than 35 years. Methods: Global miRNA expression was analyzed in breast cancer cells from young (HCC1500, HCC1937) and old patients (MCF-7, MDA-MB-231, HCC1806, and MDA-MB-468). In addition, it was compared with same type of results from patients. Results: We observed a differential profile for 155 miRNAs between young and older cell lines. We identified a set of 24 miRNA associated with aggressiveness that were regulating pluripotency of stem cell-related pathways. Combining the miRNA expression data from cell lines and breast cancer patients, 132 miRNAs were differently expressed between young and old samples, most of them previously found in cell lines. MiR-23a-downregulation was also associated with poor survival in young patients. Conclusions: Our results suggest that HCC1500 and HCC1937 cell lines could be suitable cellular models for breast cancer affecting young women. The miR-23a-downregulation could have a potential role as a poor prognosis biomarker in this age group.

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Addition of Drug-Response Specific Micro-RNAs to the International Prognostic Index Improves Prognostic Stratification of GCB-DLBCL Patients Treated with R-CHOP

Blood ◽

10.1182/blood-2019-122351 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1623-1623 ◽

Cited By ~ 1

Author(s):

Karen Dybkær ◽

Hanne Due ◽

Rasmus Froberg Brøndum ◽

Ken H. Young ◽

Martin Bøgsted

Keyword(s):

Disease Progression ◽

Cell Line ◽

Cell Lines ◽

Mirna Expression ◽

Drug Response ◽

Drug Exposure ◽

International Prognostic Index ◽

Prognostic Index ◽

Expression Data ◽

Prognostic Stratification

Background: Patients with Diffuse large B-cell lymphoma (DLBCL) in approximately 40% of cases suffer from primary refractory disease and treatment induced immuno-chemotherapy resistance demonstrating that standard provided treatment regimens are not sufficient to cure all patients. Early detection of resistance is of great importance and defining microRNA (miRNA) involvement in resistance could be useful to guide treatment selection and help monitor treatment administration while sparing patients for inefficient, but still toxic therapy. Concept and Aims: With information on drug-response specific miRNAs, we hypothesized that multi-miRNA panels can improve robustness of individual clinical markers and serve as a prognostic classifier predicting disease progression in DLBCL patients. Methods: Fifteen DLBCL cell lines were tested for sensitivity towards rituximab (R), cyclophosphamide (C), doxorubicin (H), and vincristine (O). Cell line specific seeding concentrations was used to ensure exponential growth and each cell line was subjected to 16 concentrations in serial 2-fold dilutions and number of metabolic active cells was evaluated after 48 hours of drug exposure using MTS assay. For each drug, we ranked the cell lines according to their sensitivity and categorized them as sensitive, intermediate responsive, or resistant. Differential miRNA expression analysis between sensitive and resistant cell lines identified 43 miRNAs to be associated with response to compounds of the R-CHOP regimen, by selecting probes with a log fold change larger than 2. Baseline miRNA expression data were obtained for each cell line in untreated condition, and differential miRNA expression analysis identified 43 miRNAs associated to response to R-CHOP. Using the Affymetrix HG-U133+2 platform, expression levels of the miRNA precursors were assessed in 701 diagnostic DLBCL biopsies, and miRNA-panel classifiers were build using multiple Cox regression or random survival forest. Results: Generated prognostic miRNA-panel classifiers were tested for predictive accuracies and were subsequently evaluated by Brier scores and time varying area under the ROC curves (tAUC). Progression-free survival (PFS) was chosen as the outcome, since it is a treatment evaluation parameter as closely as possible to the time of drug exposure and the tested miRNAs were all associated directly to drug specific response. Furthermore, overall survival (OS) was used for verification of findings. Comparison of analyses conducted for the respective cohorts (All DLBCL, ABC, and GCB patients) showed the lowest prediction errors for all models within the GCB subclass with a multivariate Cox miRNA-panel model including miR-146a, miR-155, miR-21, miR-34a, and miR-23a~miR-27a~miR-24-2 cluster performed the best and successfully stratified GCB-DLBCL patients into high- and low-risk of disease progression. In addition, combination of the miRNA-panel and international prognostic index (IPI) substantially increased prognostic performance in GCB classified patients, indicating a prognostic signal from the response-specific miRNAs independent of IPI. In conclusion: We found as proof of concept that adding gene expression data detecting drug-response specific miRNAs to the clinically established IPI improved the prognostic stratification of GCB-DLBCL patients treated with R-CHOP. Disclosures No relevant conflicts of interest to declare.

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Multidrug resistance-1 and p-glycoprotein in human chondrosarcoma cell lines: Expression correlates with decreased intracellular doxorubicin andin vitro chemoresistance

Journal of Orthopaedic Research® ◽

10.1002/jor.1100170619 ◽

1999 ◽

Vol 17 (6) ◽

pp. 935-940 ◽

Cited By ~ 42

Author(s):

James J. Wyman ◽

Abby M. Hornstein ◽

Patricia A. Meitner ◽

Solida Mak ◽

Patrick Verdier ◽

...

Keyword(s):

Multidrug Resistance ◽

Cell Lines ◽

Chondrosarcoma Cell ◽

Human Chondrosarcoma ◽

P Glycoprotein

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mirEX: a platform for comparative exploration of plant pri-miRNA expression data

Nucleic Acids Research ◽

10.1093/nar/gkr878 ◽

2011 ◽

Vol 40 (D1) ◽

pp. D191-D197 ◽

Cited By ~ 31

Author(s):

Dawid Bielewicz ◽

Jakub Dolata ◽

Andrzej Zielezinski ◽

Sylwia Alaba ◽

Bogna Szarzynska ◽

...

Keyword(s):

Mirna Expression ◽

Expression Data ◽

Mirna Expression Data

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A novel orthotopic animal model of human chondrosarcoma

Osteologie/Osteology ◽

10.1055/s-0037-1621964 ◽

2012 ◽

Vol 21 (04) ◽

pp. 296-300

Author(s):

K. Horas ◽

M. Tonak ◽

A. A. Kurth

Keyword(s):

Animal Model ◽

Cell Lines ◽

Bone Tumour ◽

In Vivo Studies ◽

Preclinical Model ◽

Orthotopic Implantation ◽

Chondrosarcoma Cell ◽

Human Chondrosarcoma

SummaryChondrosarcoma is the second most common primary malignant bone tumour in humans. Currently, surgical resection is the only appropriate curative approach as it is relatively unresponsive to traditional chemoand radiotherapy. However, a complete resection is often hindered due to the proximity to organs resulting in a poor outcome of this challenging malignancy. Few novel antitumour agents have been tested on different chondrosarcoma cell lines in vitro so far. In order to qualify new agents in vivo, animal models are often used in which cell lines are subcutaneously injected prior to chemotherapeutical treatment. These types of models often lack relevance to the human chondrosarcoma as the number of agents that fail in the clinic far outweighs those considered effective on in vivo studies. Orthotopic xenograft models however are of much more predictive value. Thus, the development of a novel orthotopic animal model for human chondrosarcoma using a three-dimensional matrix carrying tumour cells, was the aim of this study. For that purpose, SW-1353, a human bone chondrosarcoma cell line, was first cultured in MatrigelTM, followed by orthotopic implantation into10 SCID mice by intra-tibial injection. After 40 days, the animals developed localized bone tumours verified by radiographic and histological examinations. Radiologic and histological sections showed osteolysis and invasive tumour growth. This study demonstrates a promising new method for effective and reproducible orthotopic implantation of human chondrosarcoma. The presented animal model allows further examination and can be used as a predictive preclinical model for anticancer drug activity in humans.

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MLN4924, a Protein Neddylation Inhibitor, Suppresses the Growth of Human Chondrosarcoma through Inhibiting Cell Proliferation and Inducing Endoplasmic Reticulum Stress-Related Apoptosis

International Journal of Molecular Sciences ◽

10.3390/ijms20010072 ◽

2018 ◽

Vol 20 (1) ◽

pp. 72 ◽

Cited By ~ 5

Author(s):

Meng-Huang Wu ◽

Ching-Yu Lee ◽

Tsung-Jen Huang ◽

Kuo-Yuan Huang ◽

Chih-Hsin Tang ◽

...

Keyword(s):

Cell Proliferation ◽

Endoplasmic Reticulum ◽

Mouse Model ◽

Cell Viability ◽

Er Stress ◽

Cell Lines ◽

Cell Cycles ◽

Chondrosarcoma Cell ◽

Xenograft Mouse Model ◽

Human Chondrosarcoma

Chondrosarcoma, a heterogeneous malignant bone tumor, commonly produces cartilage matrix, which generally has no response to conventional therapies. Studies have reported that MLN4924, a NEDD8-activating enzyme inhibitor, achieves antitumor effects against numerous malignancies. In this study, the suppressive effects of MLN4924 on human chondrosarcoma cell lines were investigated using in vitro and in vivo assays, which involved measuring cell viability, cytotoxicity, apoptosis, proliferation, cell cycles, molecule-associated cell cycles, apoptosis, endoplasmic reticulum (ER) stress, and tumor growth in a xenograft mouse model. Our results demonstrated that MLN4924 significantly suppressed cell viability, exhibited cytotoxicity, and stimulated apoptosis through the activation of caspase-3 and caspase-7 in chondrosarcoma cell lines. Furthermore, MLN4924 significantly inhibited cell proliferation by diminishing the phosphorylation of histone H3 to cause G2/M cell cycle arrest. In addition, MLN4924 activated ER stress–related apoptosis by upregulating the phosphorylation of c-Jun N-terminal kinase (JNK), enhancing the expression of GRP78 and CCAAT-enhancer-binding protein homologous protein (CHOP, an inducer of endoplasmic ER stress–related apoptosis) and activating the cleavage of caspase-4. Moreover, MLN4924 considerably inhibited the growth of chondrosarcoma tumors in a xenograft mouse model. Finally, MLN4924-mediated antichondrosarcoma properties can be accompanied by the stimulation of ER stress–related apoptosis, implying that targeting neddylation by MLN4924 is a novel therapeutic strategy for treating chondrosarcoma.

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