Identification of MicroRNAs with Altered Expression Profiles in a Rat Model of Experimentally Induced Early Cerebral Aneurysms

The common water-soluble organic germanium compound poly-trans-[(2-carboxyethyl) germasesquioxane] (Ge-132) exhibits activities related to immune responses and antioxidant induction. In this study, we evaluated the antioxidative effect of dietary Ge-132 in the plasma of mice. Male ICR mice (seven mice per group) received an AIN-76 diet with 0.05 % Ge-132; three groups received the Ge-132-containing diet for 0, 1 or 4 days. The plasma alpha-tocopherol (α-tocopherol) concentration increased from 6.85 to 9.60 μg/ml after 4 days of Ge-132 intake (p < 0.05). We evaluated the changes in hepatic gene expression related to antioxidative activity as well as in the entire expression profile after one day of Ge-132 intake, using DNA microarray technology. We identified 1,220 genes with altered expression levels greater than 1.5-fold (increased or decreased) as a result of Ge-132 intake, and α-tocopherol transfer protein (Ttpa) gene expression was increased 1.62-fold. Immune activation was identified as the category with the most changes (containing 60 Gene Ontology (GO) term biological processes (BPs), 41 genes) via functional clustering analysis of altered gene expression. Ge-132 affected genes in clusters related to ATP production (22 GO term BPs, 21 genes), lipid metabolism (4 GO term BPs, 38 genes) and apoptosis (5 GO term BPs). Many GO term BPs containing these categories were significantly affected by the Ge-132 intake. Oral Ge-132 intake may therefore have increased plasma α-tocopherol levels by up-regulating α-tocopherol transfer protein (Ttpa) gene expression.

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Faculty Opinions recommendation of Long noncoding RNA expression profiles of hypoxic pulmonary hypertension rat model.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726052187.793513050 ◽

2016 ◽

Author(s):

Lars C Huber

Keyword(s):

Pulmonary Hypertension ◽

Rat Model ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Expression Profiles ◽

Rna Expression ◽

Hypoxic Pulmonary Hypertension

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The circular RNA circSlc7a11 promotes bone cancer pain pathogenesis in rats by modulating LLC-WRC 256 cell proliferation and apoptosis

Molecular and Cellular Biochemistry ◽

10.1007/s11010-020-04020-1 ◽

2021 ◽

Author(s):

Han-Wen Chen ◽

Xiao-Xia Zhang ◽

Zhu-Ding Peng ◽

Zu-Min Xing ◽

Yi-Wen Zhang ◽

...

Keyword(s):

Cell Proliferation ◽

Cancer Pain ◽

Expression Profiles ◽

Bone Cancer ◽

Circular Rna ◽

Differentially Expressed ◽

Bone Cancer Pain ◽

Circular Rnas ◽

Altered Expression ◽

Proliferation And Apoptosis

AbstractTreatment of bone cancer pain (BCP) caused by bone metastasis in advanced cancers remains a challenge in clinical oncology, and the underlying mechanisms of BCP are poorly understood. This study aimed to investigate the pathogenic roles of circular RNAs (circRNAs) in regulating cancer cell proliferation and BCP development. Eight differentially expressed circRNAs in the rat spinal cord were validated by agarose gel electrophoresis and Sanger sequencing. Expression of circRNAs and mRNAs was detected by quantitative RT-PCR. MTS assay and flow cytometry were performed to analyze cell proliferation and apoptosis, respectively. Differentially expressed mRNA profiles were characterized by deep RNA sequencing, hierarchical clustering, and functional categorization. The interactions among circRNAs, microRNAs (miRNAs), and mRNAs were predicted using TargetScan. Additionally, western blot was performed to determine the protein levels of Pax8, Isg15, and Cxcl10. Multiple circRNAs were differentially expressed in the spinal cords of BCP model rats; of these, circSlc7a11 showed the greatest increase in expression. The overexpression of circSlc7a11 significantly promoted cell proliferation and repressed apoptosis of LLC-WRC 256 and UMR-106 cells, whereas circSlc7a11 silencing produced the opposite effects. Altered expression of circSlc7a11 also induced substantial changes in the mRNA expression profiles of LLC-WRC 256 cells; these changes were linked to multiple apoptotic processes and signaling pathways, such as the chemokine signaling pathway, and formed a complex circRNA/miRNA/mRNA network. Additionally, Pax8, Isg15, and Cxc110 protein level in LLC-WRC 256 cells was consistent with the mRNA results. The circRNA circSlc7a11 regulates rat BCP development by modulating LLC-WRC 256 cell proliferation and apoptosis through multiple-signaling mechanisms.

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Molecular Factors and Biochemical Pathways Induced by Febrile Temperature in Intraerythrocytic Plasmodium falciparum Parasites

Infection and Immunity ◽

10.1128/iai.01236-06 ◽

2007 ◽

Vol 75 (4) ◽

pp. 2012-2025 ◽

Cited By ~ 83

Author(s):

Miranda S. M. Oakley ◽

Sanjai Kumar ◽

Vivek Anantharaman ◽

Hong Zheng ◽

Babita Mahajan ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Elevated Temperature ◽

Profile Analysis ◽

Expression Profiles ◽

Febrile Illness ◽

Dependent Manner ◽

Sequence Profile ◽

Host Cell Membrane ◽

Altered Expression ◽

Parasite Survival

ABSTRACT Intermittent episodes of febrile illness are the most benign and recognized symptom of infection with malaria parasites, although the effects on parasite survival and virulence remain unclear. In this study, we identified the molecular factors altered in response to febrile temperature by measuring differential expression levels of individual genes using high-density oligonucleotide microarray technology and by performing biological assays in asexual-stage Plasmodium falciparum parasite cultures incubated at 37°C and 41°C (an elevated temperature that is equivalent to malaria-induced febrile illness in the host). Elevated temperature had a profound influence on expression of individual genes; 336 of approximately 5,300 genes (6.3% of the genome) had altered expression profiles. Of these, 163 genes (49%) were upregulated by twofold or greater, and 173 genes (51%) were downregulated by twofold or greater. In-depth sensitive sequence profile analysis revealed that febrile temperature-induced responses caused significant alterations in the major parasite biologic networks and pathways and that these changes are well coordinated and intricately linked. One of the most notable transcriptional changes occurs in genes encoding proteins containing the predicted Pexel motifs that are exported into the host cytoplasm or inserted into the host cell membrane and are likely to be associated with erythrocyte remodeling and parasite sequestration functions. Using our sensitive computational analysis, we were also able to assign biochemical or biologic functional predictions for at least 100 distinct genes previously annotated as “hypothetical.” We find that cultivation of P. falciparum parasites at 41°C leads to parasite death in a time-dependent manner. The presence of the “crisis forms” and the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling-positive parasites following heat treatment strongly support the notion that an apoptosis-like cell death mechanism might be induced in response to febrile temperatures. These studies enhance the possibility of designing vaccines and drugs on the basis of disruption in molecules and pathways of parasite survival and virulence activated in response to febrile temperatures.

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Salivary MicroRNAs for Early Detection of Head and Neck Squamous Cell Carcinoma: A Case-Control Study in the High Altitude Mestizo Ecuadorian Population

BioMed Research International ◽

10.1155/2018/9792730 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 9

Author(s):

Carolina Salazar-Ruales ◽

Jessica-Viviana Arguello ◽

Andrés López-Cortés ◽

Alejandro Cabrera-Andrade ◽

Jennyfer M. García-Cárdenas ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

High Altitude ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Expression Profiles ◽

Neck Squamous Cell Carcinoma ◽

Altered Expression ◽

Mortality And Morbidity ◽

Tumor Stages

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer with the highest incidence worldwide. HNSCC is often diagnosed at advanced stages, incurring significant high mortality and morbidity. The use of saliva, as a noninvasive tool for the diagnosis of cancer, has recently increased. Salivary microRNAs (miRNAs) have emerged as a promising molecular tool for early diagnosis of HNSCC. The aim was to identify the differential expression of salivary miRNAs associated with HNSCC in the high altitude mestizo Ecuadorian population. Using PCR Arrays, miR-122-5p, miR-92a-3p, miR-124-3p, miR-205-5p, and miR-146a-5p were found as the most representative ones. Subsequently, miRNAs expression was confirmed in saliva samples from 108 cases and 108 controls. miR-122-5p, miR-92a-3p, miR-124-3p, and miR-146a-5p showed significant statistical difference between cases and controls with areas under the curve (AUC) of 0.73 (p < 0.001), 0.70 (p < 0.001), 0.71 (p = 0.002), and 0.66 (p = 0.008), respectively. miRNAs were also deregulated in between HNSCC localizations. A differentiated expression of miR-122-5p between oral cancer and oropharynx cancer (AUC of 0.96 p = 0.01) was found: miR-124-3p between larynx and pharynx (AUC = 0.97, p < 0.01) and miR-146a-5p between larynx, oropharynx, and oral cavity (AUC = 0.96, p = 0.01). Moreover, miR-122-5p, miR-124-3p, miR-205-5p, and miR-146a-5p could differentiate between HPV+ and HPV- (p=0.004). Finally, the expression profiles of the five miRNAs were evaluated to discriminate HNSCC patient’s tumor stages (TNM 2-4). miR-122-5p differentiates TNM 2 and 3 (p = 0.002, AUC = 0.92), miR-124-3p TNM 2, 3, and 4 (p < 0.001, AUC = 98), miR-146a-5p TNM 2 and 3 (p < 0.001, AUC = 0.97), and miR-92a-3p TNM 3 (p < 0.001, AUC = 0.99). Taken together, these findings show that altered expression of miRNAs could be used as biomarkers for HNSCC diagnosis in the high altitude mestizo Ecuadorian population.

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Dose-response relationships in gene expression profiles in a harbor seal B lymphoma cell line exposed to 17α-ethinyl estradiol

Journal of Xenobiotics ◽

10.4081/xeno.2017.6702 ◽

2017 ◽

Vol 7 (1) ◽

Author(s):

Christine Kleinert ◽

Matthieu Blanchet ◽

François Gagné ◽

Michel Fournier

Keyword(s):

Gene Expression ◽

Cell Line ◽

Ethinyl Estradiol ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Harbor Seal ◽

Lymphoma Cell ◽

Lymphoma Cell Line ◽

Altered Expression ◽

B Lymphoma

The determination of changes in gene expression profiles with xenobiotic dose will allow identifying biomarkers and modes of toxicant action. The harbor seal (Phoca vitulina) 11B7501 B lymphoma cell line was exposed to 1, 10, 100, 1000, 10,000, or 25,000 μg/L 17α-ethinyl estradiol (EE2, the active compound of the contraceptive pill) for 24 h. Following exposure, RNA was extracted and transformed into cDNA. Transcript expression in exposed vs. control lymphocytes was analyzed via RT-qPCR to identify genes with altered expression. Our analysis indicates that gene expression for all but the reference gene varied with dose, suggesting that different doses induce distinct physiological responses. These findings demonstrate that RT-qPCR could be used to identify immunotoxicity and relative dose in harbor seal leukocytes.

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In Vitro Measures Used to Predict Anticancer Activity of Apple Cultivars and Their Comparison to Outcomes From a Rat Model of Experimentally Induced Breast Cancer

Nutrition and Cancer ◽

10.1080/01635580902825563 ◽

2009 ◽

Vol 61 (4) ◽

pp. 510-517 ◽

Cited By ~ 7

Author(s):

Matthew D. Thompson ◽

Cecil Stushnoff ◽

John N. McGinley ◽

Henry J. Thompson

Keyword(s):

Breast Cancer ◽

Anticancer Activity ◽

Rat Model ◽

Apple Cultivars ◽

Experimentally Induced

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Circular RNA Hsa_Circ_0091579 Serves as a Diagnostic and Prognostic Marker for Hepatocellular Carcinoma

Cellular Physiology and Biochemistry ◽

10.1159/000495230 ◽

2018 ◽

Vol 51 (1) ◽

pp. 290-300 ◽

Cited By ~ 18

Author(s):

Chenxing Zhang ◽

Chenyue Zhang ◽

Jiamao Lin ◽

Haiyong Wang

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Tumors ◽

Expression Profiles ◽

Critical Role ◽

Roc Curves ◽

Altered Expression ◽

Qrt Pcr ◽

Specificity And Sensitivity ◽

Tumor Tissues ◽

Potential Biomarker

Background/Aims: An increasing number of studies have suggested that circular RNAs (circRNAs) have vital roles in carcinogenesis and tumor progression. However, the function of circRNAs in hepatocellular carcinoma (HCC) remains poorly characterized. Methods: We investigated the levels of circRNAs in patients with HCC to identify potential diagnostic biomarkers. We examined circRNA expression profiles in liver tumors and paired non-cancerous liver tissues from three HCC patients with cancer thrombus using a circRNA microarray. Bioinformatics analysis was performed to find circRNAs with significantly altered expression levels between tumors and their paired non-tumor tissues. We confirmed our initial findings by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Receiver operating characteristic (ROC) curves were also applied to identify a candidate circRNA with the optimal specificity and sensitivity. Finally, X-tile software was adopted to calculate the most efficient cut-off value for hsa_circ_0091579 expression. Results: Microarray analysis identified 20 unique circRNAs that were differentially expressed between tumor and non-tumor tissues (P < 0.05). The expression of these 20 circRNAs was verified by qRT-PCR. The expression of hsa_circ_16245-1 and hsa_circ_0091579 mRNA was consistent with their levels as tested by the microarray. The ROC curves showed that both hsa_circ_16245-1 and hsa_circ_0091579 had favorable specificity and sensitivity. We further confirmed that hsa_circ_0091579 was significantly upregulated in HCC and its high expression was intimately associated with a worse overall survival in patients with HCC. Conclusion: Hsa_circ_0091579 may play a critical role in HCC progression and serve as a potential biomarker for the prognosis of patients with HCC.

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