scholarly journals Lung Adenocarcinoma Transcriptomic Analysis Predicts Adenylate Kinase Signatures Contributing to Tumor Progression and Negative Patient Prognosis

Metabolites ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 859
Author(s):  
Jonathan A. Chacon-Barahona ◽  
Ivan A. Salladay-Perez ◽  
Nathan James Lanning
Keyword(s):  
Lung Adenocarcinoma ◽  
Tumor Progression ◽  
Gene Networks ◽  
Regulatory Gene ◽  
Nucleotide Metabolism ◽  
Transcriptomic Analysis ◽  
Metabolic Reprogramming ◽  
Altered Expression ◽  
Gene Signatures ◽  
Tumor Stages

The ability to detect and respond to hypoxia within a developing tumor appears to be a common feature amongst most cancers. This hypoxic response has many molecular drivers, but none as widely studied as Hypoxia-Inducible Factor 1 (HIF-1). Recent evidence suggests that HIF-1 biology within lung adenocarcinoma (LUAD) may be associated with expression levels of adenylate kinases (AKs). Using LUAD patient transcriptome data, we sought to characterize AK gene signatures related to lung cancer hallmarks, such as hypoxia and metabolic reprogramming, to identify conserved biological themes across LUAD tumor progression. Transcriptomic analysis revealed perturbation of HIF-1 targets to correlate with altered expression of most AKs, with AK4 having the strongest correlation. Enrichment analysis of LUAD tumor AK4 gene signatures predicts signatures involved in pyrimidine, and by extension, nucleotide metabolism across all LUAD tumor stages. To further discriminate potential drivers of LUAD tumor progression within AK4 gene signatures, partial least squares discriminant analysis was used at LUAD stage-stage interfaces, identifying candidate genes that may promote LUAD tumor growth or regression. Collectively, these results characterize regulatory gene networks associated with the expression of all nine human AKs that may contribute to underlying metabolic perturbations within LUAD and reveal potential mechanistic insight into the complementary role of AK4 in LUAD tumor development.

scholarly journals Global transcriptome profile of the developmental principles of in vitro iPSC-to-motor neuron differentiation

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Emilia Solomon ◽  
Katie Davis-Anderson ◽  
Blake Hovde ◽  
Sofiya Micheva-Viteva ◽  
Jennifer Foster Harris ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Acetylcholine Receptors ◽  
Gene Networks ◽  
Spinal Cord Injuries ◽  
Regulatory Gene ◽  
Transcriptome Profile

Abstract Background Human induced pluripotent stem cells (iPSC) have opened new avenues for regenerative medicine. Consequently, iPSC-derived motor neurons have emerged as potentially viable therapies for spinal cord injuries and neurodegenerative disorders including Amyotrophic Lateral Sclerosis. However, direct clinical application of iPSC bears in itself the risk of tumorigenesis and other unforeseeable genetic or epigenetic abnormalities. Results Employing RNA-seq technology, we identified and characterized gene regulatory networks triggered by in vitro chemical reprogramming of iPSC into cells with the molecular features of motor neurons (MNs) whose function in vivo is to innervate effector organs. We present meta-transcriptome signatures of 5 cell types: iPSCs, neural stem cells, motor neuron progenitors, early motor neurons, and mature motor neurons. In strict response to the chemical stimuli, along the MN differentiation axis we observed temporal downregulation of tumor growth factor-β signaling pathway and consistent activation of sonic hedgehog, Wnt/β-catenin, and Notch signaling. Together with gene networks defining neuronal differentiation (neurogenin 2, microtubule-associated protein 2, Pax6, and neuropilin-1), we observed steady accumulation of motor neuron-specific regulatory genes, including Islet-1 and homeobox protein HB9. Interestingly, transcriptome profiling of the differentiation process showed that Ca2+ signaling through cAMP and LPC was downregulated during the conversion of the iPSC to neural stem cells and key regulatory gene activity of the pathway remained inhibited until later stages of motor neuron formation. Pathways shaping the neuronal development and function were well-represented in the early motor neuron cells including, neuroactive ligand-receptor interactions, axon guidance, and the cholinergic synapse formation. A notable hallmark of our in vitro motor neuron maturation in monoculture was the activation of genes encoding G-coupled muscarinic acetylcholine receptors and downregulation of the ionotropic nicotinic acetylcholine receptors expression. We observed the formation of functional neuronal networks as spontaneous oscillations in the extracellular action potentials recorded on multi-electrode array chip after 20 days of differentiation. Conclusions Detailed transcriptome profile of each developmental step from iPSC to motor neuron driven by chemical induction provides the guidelines to novel therapeutic approaches in the re-construction efforts of muscle innervation.

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

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
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.

Paip1 predicts poor prognosis and promotes tumor progression through AKT/GSK-3β pathway in lung adenocarcinoma

2019 ◽  
Vol 86 ◽  
pp. 233-242 ◽  
Author(s):  
Yixuan Wang ◽  
Junjie Piao ◽  
Qianrong Wang ◽  
Xuelian Cui ◽  
Ziqi Meng ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Tumor Progression ◽  
Poor Prognosis ◽  
Gsk 3Β

scholarly journals Requirement for BUB1B/BUBR1 in tumor progression of lung adenocarcinoma

2015 ◽  
Vol 6 (3-4) ◽  
pp. 106-118 ◽  
Author(s):  
Honglin Chen ◽  
James Lee ◽  
Noelyn M. Kljavin ◽  
Benjamin Haley ◽  
Anneleen Daemen ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Tumor Progression

scholarly journals Abstract 2936: Ago2 induces Kras signaling and promotes tumor progression in mouse models of lung adenocarcinoma

2021 ◽  
Author(s):  
Jean C. Tien ◽  
Seema Chugh ◽  
Andrew E. Goodrum ◽  
Yunhui Cheng ◽  
Lisha Wang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Tumor Progression ◽  
Mouse Models

scholarly journals Modularity of the metabolic gene network as a prognostic biomarker for hepatocellular carcinoma

2017 ◽  
Author(s):  
Fengdan Ye ◽  
Dongya Jia ◽  
Mingyang Lu ◽  
Herbert Levine ◽  
Michael W Deem
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Biomarker ◽  
Malignant Tumors ◽  
Aerobic Glycolysis ◽  
Expression Patterns ◽  
Cancer Recurrence ◽  
Metabolic Reprogramming ◽  
The Cancer Genome Atlas ◽  
Driver Genes ◽  
Tumor Stages

AbstractAbnormal metabolism is an emerging hallmark of cancer. Cancer cells utilize both aerobic glycolysis and oxidative phosphorylation (OXPHOS) for energy production and biomass synthesis. Understanding the metabolic reprogramming in cancer can help design therapies to target metabolism and thereby to improve prognosis. We have previously argued that more malignant tumors are usually characterized by a more modular expression pattern of cancer-associated genes. In this work, we analyzed the expression patterns of metabolism genes in terms of modularity for 371 hepatocellular carcinoma (HCC) samples from the Cancer Genome Atlas (TCGA). We found that higher modularity significantly correlated with glycolytic phenotype, later tumor stages, higher metastatic potential, and cancer recurrence, all of which contributed to poorer prognosis. Among patients with recurred tumor, we found the correlation of higher modularity with worse prognosis during early to mid-progression. Furthermore, we developed metrics to calculate individual modularity, which was shown to be predictive of cancer recurrence and patients’ survival and therefore may serve as a prognostic biomarker. Our overall conclusion is that more aggressive HCC tumors, as judged by decreased host survival probability, had more modular expression patterns of metabolic genes. These results may be used to identify cancer driver genes and for drug design.

scholarly journals Single cell transcriptomics reveal temporal dynamics of critical regulators of germ cell fate during mouse sex determination

2019 ◽  
Author(s):  
Chloé Mayère ◽  
Yasmine Neirijnck ◽  
Pauline Sararols ◽  
Chris M Rands ◽  
Isabelle Stévant ◽  
...  
Keyword(s):  
Sex Determination ◽  
Germ Cell ◽  
Single Cell ◽  
Cell Fate ◽  
Gene Networks ◽  
Network Inference ◽  
Temporal Dynamics ◽  
Intron Retention ◽  
Gonad Development ◽  
Altered Expression

SummaryDespite the importance of germ cell (GC) differentiation for sexual reproduction, the gene networks underlying their fate remain unclear. Here, we comprehensively characterize the gene expression dynamics during sex determination based on single-cell RNA sequencing of 14,914 XX and XY mouse GCs between embryonic days (E) 9.0 and 16.5. We found that XX and XY GCs diverge transcriptionally as early as E11.5 with upregulation of genes downstream of the Bone morphogenic protein (BMP) and Nodal/Activin pathways in XY and XX GCs, respectively. We also identified a sex-specific upregulation of genes associated with negative regulation of mRNA processing and an increase in intron retention consistent with a reduction in mRNA splicing in XY testicular GCs by E13.5. Using computational gene regulation network inference analysis, we identified sex-specific, sequential waves of putative key regulator genes during GC differentiation and revealed that the meiotic genes are regulated by positive and negative master modules acting in an antagonistic fashion. Finally, we found that rare adrenal GCs enter meiosis similarly to ovarian GCs but display altered expression of master genes controlling the female and male genetic programs, indicating that the somatic environment is important for GC function. Our data is available on a web platform and provides a molecular roadmap of GC sex determination at single-cell resolution, which will serve as a valuable resource for future studies of gonad development, function and disease.

scholarly journals Aberrant Fucosylation of Saliva Glycoprotein Defining Lung Adenocarcinomas Malignancy

2021 ◽  
Author(s):  
Shuang Yang ◽  
Ziyuan Gao ◽  
Zhen Wu ◽  
Ying Han ◽  
Xumin Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Early Diagnosis ◽  
Lung Adenocarcinoma ◽  
Tumor Progression ◽  
Cancer Patients ◽  
Solid Phase ◽  
Clinical Specimens ◽  
Aberrant Glycosylation ◽  
Lung Adenocarcinomas ◽  
Core Fucosylation

Aberrant glycosylation is a hallmark of cancer found during tumorigenesis and tumor progression. Lung cancer induced by oncogene mutations has been detected in the patient's saliva, and saliva glycosylation has been altered. Saliva contains highly glycosylated glycoproteins, the characteristics of which may be related to various diseases. Therefore, elucidating cancer-specific glycosylation in the saliva of healthy, non-cancer, and cancer patients can reveal whether tumor glycosylation has unique characteristics for early diagnosis. In this work, we used a solid-phase chemoenzymatic method to study the glycosylation of saliva glycoproteins in clinical specimens. The results showed that the alpha1,6-core fucosylation of glycoproteins in cancer patients was significant increased. The fucosylation of alpha1,2 or alpha1,3 is also increased in cancer patients. We further analyzed the expression of fucosyltransferases responsible for alpha1,2, alpha1,3, alpha1,6 fucosylation. The fucosylation of the saliva of cancer patients is drastically different from that of non-cancer or health controls. These results indicate that the glycoform of saliva fucosylation distinguishes lung cancer from other diseases, and this feature has the potential to diagnose lung adenocarcinoma.

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