Evolutionary Stability Optimizer (ESO): A Novel Approach to Identify and Avoid Mutational Hotspots in DNA Sequences While Maintaining High Expression Levels

In this study, we aimed to screen out genes associated with a high risk of postoperative recurrence of lung adenocarcinoma and investigate the possible mechanisms of the involvement of these genes in the recurrence of lung adenocarcinoma. We identify Hub genes and verify the expression levels and prognostic roles of these genes. Datasets of GSE40791, GSE31210, and GSE30219 were obtained from the Gene Expression Omnibus database. Enrichment analysis of gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed for the screened candidate genes using the DAVID database. Then, we performed protein–protein interaction (PPI) network analysis through the database STRING. Hub genes were screened out using Cytoscape software, and their expression levels were determined by the GEPIA database. Finally, we assessed the relationships of Hub genes expression levels and the time of survival. Forty-five candidate genes related to a high-risk of lung adenocarcinoma recurrence were screened out. Gene ontology analysis showed that these genes were enriched in the mitotic spindle assembly checkpoint, mitotic sister chromosome segregation, G2/M-phase transition of the mitotic cell cycle, and ATP binding, etc. KEGG analysis showed that these genes were involved predominantly in the cell cycle, p53 signaling pathway, and oocyte meiosis. We screened out the top ten Hub genes related to high expression of lung adenocarcinoma from the PPI network. The high expression levels of eight genes (TOP2A, HMMR, MELK, MAD2L1, BUB1B, BUB1, RRM2, and CCNA2) were related to short recurrence-free survival and they can be used as biomarkers for high risk of lung adenocarcinoma recurrence. This study screened out eight genes associated with a high risk of lung adenocarcinoma recurrence, which might provide novel insights into researching the recurrence mechanisms of lung adenocarcinoma as well as into the selection of targets in the treatment of the disease.

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High expression levels of egfl7 correlate with low endothelial cell activation in peritumoral vessels of human breast cancer

Oncology Letters ◽

10.3892/ol.2016.4791 ◽

2016 ◽

Vol 12 (2) ◽

pp. 1422-1428 ◽

Cited By ~ 7

Author(s):

Diane Pannier ◽

Géraldine Philippin-Lauridant ◽

Marie-Christine Baranzelli ◽

Delphine Bertin ◽

Emilie Bogart ◽

...

Keyword(s):

Breast Cancer ◽

Endothelial Cell ◽

Human Breast Cancer ◽

Cell Activation ◽

High Expression ◽

Human Breast ◽

Endothelial Cell Activation ◽

Expression Levels ◽

Peritumoral Vessels

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A strategy to obtain recombinant cell lines with high expression levels. Lentiviral vector-mediated transgenesis

BMC Proceedings ◽

10.1186/1753-6561-5-s8-p7 ◽

2011 ◽

Vol 5 (S8) ◽

Cited By ~ 12

Author(s):

Claudio Prieto ◽

Diego Fontana ◽

Marina Etcheverrigaray ◽

Ricardo Kratje

Keyword(s):

Cell Lines ◽

Lentiviral Vector ◽

High Expression ◽

Expression Levels ◽

Recombinant Cell

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High Expression of ANXA2 Pseudogene ANXA2P2 Promotes an Aggressive Phenotype in Hepatocellular Carcinoma

Disease Markers ◽

10.1155/2019/9267046 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 4

Author(s):

Qiu-shuang Wang ◽

Liang-Liang Shi ◽

Fei Sun ◽

Yi-fan Zhang ◽

Ren-Wang Chen ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Disease Free Survival ◽

Annexin A2 ◽

The Cancer Genome Atlas ◽

High Expression ◽

Migration And Invasion ◽

Targeted Drugs ◽

Noncancerous Tissue ◽

Expression Levels ◽

Hcc Cells

Objective. Accumulating evidence suggests that pseudogenes play potential roles in the regulation of their cognate wild-type genes, oncogenes, and tumor suppressor genes. ANXA2P2 (annexin A2 pseudogene 2) is one of three pseudogenes of annexin A2 that have recently been shown to be aberrantly transcribed in hepatocellular carcinoma (HCC) cells. However, its clinical meaning and biological function in HCC have remained unclear. Therefore, the present study was aimed at exploring the prognostic value of a high expression of ANXA2P2 in HCC tissue and at identifying whether it can affect the efficacy of targeted drugs (sorafenib, regorafenib, and lenvatinib). Methods. We obtained ANXA2P2 mRNA expression levels from The Cancer Genome Atlas (TCGA) RNA sequence database. The expression levels of ANXA2P2 in 49 pairs of intratumoral and peritumoral liver tissues were examined by RT-PCR. Wound healing and transwell assays were performed to confirm the tumor-promoting properties of ANXA2P2 in HCC cells. CCK8 assay was conducted to identify whether ANXA2P2 can affect the growth of HCC cells when administered with targeted drugs (sorafenib, regorafenib, and lenvatinib). Results. The expression of ANXA2P2 in HCC tissues was significantly higher than that in adjacent cancerous tissues from TCGA database and validation group. Additionally, patients with high ANXA2P2 expression in HCC tissue had a shorter overall survival, whereas no statistically significant correlation was found between ANXA2P2 expression and disease-free survival (p=0.08) as well as other clinical parameters, such as age, gender, histological grade, T classification, stage, albumin level, alpha-fetoprotein, and vascular invasion (p=0.7323, 0.8807, 0.5762, 0.8515, 0.7113, 0.242, 1.0000, and 0.7685, respectively). Furthermore, in vitro experiments showed that knockdown of ANXA2P2 inhibited migration and invasion of HCC cells but did not have an influence on the HCC cell proliferation when treated with targeted drugs (sorafenib, regorafenib, and lenvatinib). Conclusion. Our study confirmed elevated ANXA2P2 expression levels in HCC tissue compared with adjacent noncancerous tissue and a worse prognosis of patients with high ANXA2P2 levels in the HCC tissue. The newly found properties of promoting migration and invasion of ANXA2P2 in HCC help to explain this phenomenon. ANXA2P2 could be a novel and suitable predicative biomarker for the risk assessment of recurrence or metastasis of HCC patients but may not be effective to predict the efficacy of targeted drugs.

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Elucidation of molecular mechanisms of flower form development in tree peony ( Paeonia suffriticosa ) through comparative transcriptome analysis of floral parts

10.21203/rs.2.18308/v1 ◽

2019 ◽

Author(s):

Jiuxing Lu ◽

Yun Zheng ◽

Haoning Wang ◽

Zheng Wang ◽

Yonghua Li ◽

...

Keyword(s):

Woody Plants ◽

Molecular Mechanisms ◽

High Expression ◽

Limited Information ◽

Mads Box ◽

Mads Box Genes ◽

Tree Peony ◽

Expression Levels ◽

Key Genes ◽

Flower Form

Abstract Background: Tree peony (Paeonia suffruticasa) is an economically, medicinally ornamentally important woody flowering woody plants in East Asia and is a common also ornamental shrub in Europe and North America. It is well known and prized for their beautiful flowers in many different forms. Samen petalody has been shown to be the most effective way to modify flower forms. However, there is limited information on the molecular mechanisms of stamen petalody and flower form formation in tree peony.Results: In this study, RNA sequencing was used to assemble and annotate the unigenes in the tree peony to identify the critical genes related to flower parts formation and verify the key genes in different flower forms of tree peony cultivar. A total of 76,007 high quality unigenes were assembled and 30,505 were successfully annotated. A total of 1,833 TFs were identified in our study, among them 16 MADS-box genes were found and characterized. Six key genes were selected to verity their functions in stamen petalody. AG and SEP showed high expression level in carpals and sepals separately both in stamen petalody group and non-stamen petalody groups. PI and AP3 showed high expression levels in inter-petals in stamen petalody groups than in staments in non-stamen petalody.Conclusion: Sixteen MADS-box genes were identified for the first time in tree peony through RNA-seq method. We identified six key genes based on their differential expression levels in different flower parts. These six key genes represented all categories in the ABCDE model to verify the functions in stamen petalody. PI and AP3 were verified to likely play important roles in regulating stamen petalody in tree peony. Our study has helped establish the flower development model in tree peony, identified key molecular mechanisms in the development of different flower forms, and provided valuable information in improving genetic diversity of tree peony and many other woody plants.

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Circular RNA hsa_circ_0005046 and hsa_circ_0001791 May Become Diagnostic Biomarkers for Breast Cancer Early Detection

Journal of Oncology ◽

10.1155/2021/2303946 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Melika Ameli-Mojarad ◽

Mandana Ameli-Mojarad ◽

Mitra Nourbakhsh ◽

Ehsan Nazemalhosseini-Mojarad

Keyword(s):

Breast Cancer ◽

Roc Curve ◽

Expression Profiles ◽

Circular Rna ◽

Diagnostic Value ◽

High Expression ◽

Expression Level ◽

Diagnostic Biomarker ◽

Expression Levels ◽

Normal Tissues

Breast cancer (BC) is one of the most common lethal diseases in women worldwide. Recent evidence has shown that covalently closed Circular RNA (circRNA) deregulation is observed in different human malignancies and cancers. Lately, circRNAs are being considered as a new diagnostic biomarker; however, the mechanism and the correlation of action between circRNAs and BC are still unclear. In the present study, we try to investigate the expression level of hsa_circ_0005046 and hsa_circ_0001791 in BC. By using quantitative real-time polymerase chain reaction (qRT-PCR), expression profiles of candidate circRNAs were detected in 60 BC tissue and paired adjacent normal tissues. Furthermore, the clinicopathological relation and diagnostic value were estimated. Our results showed the higher expression levels of hsa_circ_0005046 and hsa_circ_0001791 in BC tissues compared to paired adjacent normal tissues with P value ( P < 0.0001 ) for both circRNAs, and the area under the receiver operating characteristic (ROC) curve was 0.857 and 1.0, respectively; in addition, a total 10 miRNAs that can be targeted by each candidate circRNAs was predicted base on bioinformatics databases. Taken together, for the first time, the results of our study presented high expression levels of hsa_circ_0005046 and hsa_circ_00017916 in BC; although there was no direct correlation between the high expression level of both circRNAs with clinic pathological factors, except hsa_circ_0001791 association with estrogen receptors (ER), high ROC curve in expressed samples indicated that both circRNAs could be used as a new diagnostic biomarker for BC. Moreover, miRNAs selection tools predicted that miR-215 and mir-383-5p which have a tumor suppressor role in BC can be targeted by our candidate circRNAs to affect the PI3K/AKT pathway; in conclusion, further studies are required to validate the oncogene role of our candidate circRNAs through the PI3k pathway.

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COMPARING VIRUS CLASSIFICATION USING GENOMIC MATERIALS ACCORDING TO DIFFERENT TAXONOMIC LEVELS

Journal of Bioinformatics and Computational Biology ◽

10.1142/s0219720013430038 ◽

2013 ◽

Vol 11 (06) ◽

pp. 1343003 ◽

Cited By ~ 4

Author(s):

JING-DOO WANG

Keyword(s):

Molecular Biology ◽

Dna Sequences ◽

Protein Sequences ◽

Experimental Results ◽

Virus Classification ◽

Taxonomic Level ◽

Biological Classification ◽

Novel Approach

In this paper, three genomic materials — DNA sequences, protein sequences, and regions (domains) are used to compare methods of virus classification. Virus classes (categories) are divided by various taxonomic level of virus into three datasets for 6 order, 42 family, and 33 genera. To increase the robustness and comparability of experimental results of virus classification, the classes are selected that contain at least 10 instances, and meanwhile each instance contains at least one region name. Experimental results show that the approach using region names achieved the best accuracies — reaching 99.9%, 97.3%, and 99.0% for 6 orders, 42 families, and 33 genera, respectively. This paper not only involves exhaustive experiments that compare virus classifications using different genomic materials, but also proposes a novel approach to biological classification based on molecular biology instead of traditional morphology.

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Abstract 358: First Trimester Human Umbilical Cord Perivascular Cells (FTM HUCPVCs) Maintain High Expression Levels of Angiogenic Factors and Have Superior Pro-angiogenic Effects on Endothelial Networks When Compared to Term HUCPVCs and BMSCs in an ex-vivo Rat Aortic Ring Assay

Circulation Research ◽

10.1161/res.119.suppl_1.358 ◽

2016 ◽

Vol 119 (suppl_1) ◽

Author(s):

Farwah Iqbal ◽

Peter Szaraz ◽

Shlomit Kenigsberg ◽

Andree Gauthier-Fisher ◽

Clifford Librach

Keyword(s):

Ex Vivo ◽

Human Growth ◽

Aortic Ring ◽

Angiogenic Factors ◽

High Expression ◽

Loop Formation ◽

Expression Levels ◽

Vascular Regeneration ◽

Aortic Ring Assay ◽

Qpcr Array

Introduction: Features of an ideal cell type, that would be conducive to vascular regeneration include (1) expression of pro-angiogenic genes (2) secretion of factors that promote developing or regenerating vasculature, and (3) maintenance of pro-angiogenic properties in the microvascular niche. Hypothesis: FTM HUCPVCs, a young rich source of mesenchymal stromal-like cells (MSCs) are ideal candidates for vascular regeneration due to their high expression of pro-angiogenic factors. Methods: The paracrine angiogenic potential of 3 types of MSCs was evaluated and compared using ex vivo tissue culture of rat aortic rings. Aorta sections were embedded into Matrigel™, cells were added to transwell membranes (pore=0.1μm, EBM 2% FBS) and combined with aortic rings (Day 0). Radial network growth and total loop formation were monitored by microscopy. Endothelial networks were quantified by ImageJ TM software. p values were calculated using ANOVA. (N=3 experiments, n=3 replicates). At day 7, the MSCs were isolated from transwells, human cytokine gene expression levels were measured using human growth factor profiler qPCR array (Qiagen, normalizers: GAPDH, βACT). Ct>35 considered negligible. Results: In the transwell aortic ring assay, FTM HUCPVCs induced significantly greater network growths when compared to term HUCPVCs (p≤0.0001), BMSCs (p≤0.0001) and untreated rings (p≤0.05). Quantification of network loop formation showed that FTM HUCPVCs induced greater numbers of closed loops when compared to term HUCPVCs (p≤0.0001), BMSCs (p≤0.0001) and untreated networks (p≤0.0001). Human growth factor qPCR array showed a high expression of angiogenic factors (Ct<25 cycle) both at day0 and day7 of co-culture, including BMP1, GDNF, MDK, NRG1, PDGFc, VEGFa, and VEGFc. Most cytokine expression levels were maintained up to 7 days in co-culture with 1 gene upregulated (BMP6 ΔCt>3), and 3 downregulated genes (FGF19, FGF9, NRTN ΔCt>3) at day 7 when compared to day 1. Conclusion: Compared to older sources of MSCs, FTM HUCPVCs promote developing endothelial networks in vitro via paracrine mechanisms and maintain the high expression of pro-angiogenic factors when cultures with endothelial cells.

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