scholarly journals Genome edited colorectal cancer organoid models reveal distinct microRNA activity patterns across different mutation profiles

2021 ◽  
Author(s):  
Jonathan W Villanueva ◽  
Lawrence Kwong ◽  
Teng Han ◽  
Salvador Alonso Martinez ◽  
Fong Cheng Pan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Genetically Modified ◽  
Activity Patterns ◽  
Expression Patterns ◽  
Regulatory Mechanisms ◽  
Oncogenic Mutations ◽  
Gene Regulatory ◽  
Insight Into

Somatic mutations drive colorectal cancer (CRC) by disrupting gene regulatory mechanisms. Distinct combinations of mutations can result in unique changes to regulatory mechanisms leading to variability in the efficacy of therapeutics. MicroRNAs are important regulators of gene expression, and their activity can be altered by oncogenic mutations. However, it is unknown how distinct combinations of CRC-risk mutations differentially affect microRNAs. Here, using genetically-modified mouse intestinal organoid (enteroid) models, we identify ten different modules of microRNA expression patterns across distinct combinations of mutations common in CRC. We also show that miR-24-3p, which is aberrant in genetically-modified mouse enteroids and human colonoids irrespective of mutational context, is a master regulator of gene expression in CRC. In follow-up experiments, we also demonstrate that miR-24 promotes CRC cell survival. These findings offer insight into the mechanisms that drive inter-tumor heterogeneity and highlight candidate microRNA therapeutic targets for the advancement of precision medicine for CRC.

scholarly journals Comparative transcriptomics identifies differences in the regulation of the floral transition between Arabidopsis and Brassica rapa cultivars

2020 ◽  
Author(s):  
Alexander Calderwood ◽  
Jo Hepworth ◽  
Shannon Woodhouse ◽  
Lorelei Bilham ◽  
D. Marc Jones ◽  
...  
Keyword(s):  
Gene Expression ◽  
Brassica Rapa ◽  
Regulatory Networks ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Detailed Comparison ◽  
Developmental Time ◽  
Floral Transition ◽  
Gene Regulatory

AbstractThe timing of the floral transition affects reproduction and yield, however its regulation in crops remains poorly understood. Here, we use RNA-Seq to determine and compare gene expression dynamics through the floral transition in the model species Arabidopsis thaliana and the closely related crop Brassica rapa. A direct comparison of gene expression over time between species shows little similarity, which could lead to the inference that different gene regulatory networks are at play. However, these differences can be largely resolved by synchronisation, through curve registration, of gene expression profiles. We find that different registration functions are required for different genes, indicating that there is no common ‘developmental time’ to which Arabidopsis and B. rapa can be mapped through gene expression. Instead, the expression patterns of different genes progress at different rates. We find that co-regulated genes show similar changes in synchronisation between species, suggesting that similar gene regulatory sub-network structures may be active with different wiring between them. A detailed comparison of the regulation of the floral transition between Arabidopsis and B. rapa, and between two B. rapa accessions reveals different modes of regulation of the key floral integrator SOC1, and that the floral transition in the B. rapa accessions is triggered by different pathways, even when grown under the same environmental conditions. Our study adds to the mechanistic understanding of the regulatory network of flowering time in rapid cycling B. rapa under long days and highlights the importance of registration methods for the comparison of developmental gene expression data.

scholarly journals Three Years Follow-Up Study Showed Prenatal Methamphetamine Exposure May Cause Chronic Abnormalities In Transcriptomic Pattern

2021 ◽  
Author(s):  
Arvin Haghighatfard ◽  
Soha Seifollahi ◽  
Pegah Rajabi ◽  
Niloofar Rahmani ◽  
Rojin Ghannadzadeh
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Rna Extraction ◽  
Childbearing Age ◽  
Methamphetamine Use ◽  
Methamphetamine Use Disorder

Abstract Background: The high rate of methamphetamine use disorder among young adults and women of childbearing age makes it imperative to clarify the long-term effects of Methamphetamine exposure on the offspring. Behavioral and cognitive problems had been reported in children with parental Methamphetamine exposure (PME). The present study aimed to assess the acute and chronic effects of PME in molecular regulations and gene expression profiles of children during their first years of life.Methods: All subjects were recruited before birth, and sampling was conducted from the first ten days of birth, twelve months, twenty months, and thirty-six months of age. Finally, 2658 children with PME and 3573 normal children had been finished the follow-up. RNA extraction was operated from blood samples and gene expression profiling was conducted by using the Affymetrix GeneChip Human Genome U133 plus 2.0 Array Platform. Gene expression data were confirmed by Real-time PCR. Results: Gene expression profiling during thirty-six months showed several constant mRNA level alterations in children with PME compared with normal. These genes are involved in several gene ontologies and pathways involved with the immune system, neuronal functions, and bioenergetic metabolism. It seems that Methamphetamine use disorder before and during the pregnancy period may affect the expression profile of children, and these changes could remain years after birth. Affected genes have some similarities with the gene expression patterns of addiction, psychiatric disorders, neurodevelopmental disabilities, and immune deficiencies. Conclusion: Findings may shed light on the molecular effects of prenatal methamphetamine exposure and may lead to new psychological and somatic caring protocols for these children based on their potential abnormalities.

scholarly journals Transcriptome Profiling of Adipose Tissue Reveals Depot-Specific Metabolic Alterations Among Patients with Colorectal Cancer

2019 ◽  
Vol 104 (11) ◽  
pp. 5225-5237 ◽  
Author(s):  
Mariam Haffa ◽  
Andreana N Holowatyj ◽  
Mario Kratz ◽  
Reka Toth ◽  
Axel Benner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Adipose Tissue ◽  
Large Scale ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Human Study ◽  
Subcutaneous Fat ◽  
Specific Gene ◽  
Adipose Tissue Depots

Abstract Context Adipose tissue inflammation and dysregulated energy homeostasis are key mechanisms linking obesity and cancer. Distinct adipose tissue depots strongly differ in their metabolic profiles; however, comprehensive studies of depot-specific perturbations among patients with cancer are lacking. Objective We compared transcriptome profiles of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) from patients with colorectal cancer and assessed the associations of different anthropometric measures with depot-specific gene expression. Design Whole transcriptomes of VAT and SAT were measured in 233 patients from the ColoCare Study, and visceral and subcutaneous fat area were quantified via CT. Results VAT compared with SAT showed elevated gene expression of cytokines, cell adhesion molecules, and key regulators of metabolic homeostasis. Increased fat area was associated with downregulated lipid and small molecule metabolism and upregulated inflammatory pathways in both compartments. Comparing these patterns between depots proved specific and more pronounced gene expression alterations in SAT and identified unique associations of integrins and lipid metabolism–related enzymes. VAT gene expression patterns that were associated with visceral fat area poorly overlapped with patterns associated with self-reported body mass index (BMI). However, subcutaneous fat area and BMI showed similar associations with SAT gene expression. Conclusions This large-scale human study demonstrates pronounced disparities between distinct adipose tissue depots and reveals that BMI poorly correlates with fat mass–associated changes in VAT. Taken together, these results provide crucial evidence for the necessity to differentiate between distinct adipose tissue depots for a correct characterization of gene expression profiles that may affect metabolic health of patients with colorectal cancer.

DNA copy number alterations, gene expression changes and disease-free survival in patients with colorectal cancer: a 10 year follow-up

2016 ◽  
Vol 39 (6) ◽  
pp. 545-558 ◽  
Author(s):  
Elisabetta Bigagli ◽  
Carlotta De Filippo ◽  
Cinzia Castagnini ◽  
Simona Toti ◽  
Francesco Acquadro ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Copy Number ◽  
Disease Free Survival ◽  
Copy Number Alterations ◽  
Dna Copy Number ◽  
Free Survival ◽  
Dna Copy Number Alterations ◽  
Disease Free

scholarly journals Expression Analysis of XTH in Stem Swelling of Stem Mustard and Selection of Reference Genes

Genes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 113 ◽  
Author(s):  
Mengyao Li ◽  
Fangjie Xie ◽  
Qi He ◽  
Jie Li ◽  
Jiali Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reference Genes ◽  
Expression Patterns ◽  
Regulatory Mechanisms ◽  
Future Research ◽  
Transcriptome Data ◽  
Accurate Analysis ◽  
Report Analysis ◽  
The Stability ◽  
Selection Of

Accurate analysis of gene expression requires selection of appropriate reference genes. In this study, we report analysis of eight candidate reference genes (ACTIN, UBQ, EF-1α, UBC, IF-4α, TUB, PP2A, and HIS), which were screened from the genome and transcriptome data in Brassica juncea. Four statistical analysis softwares geNorm, NormFinder, BestKeeper, and RefFinder were used to test the reliability and stability of gene expression of the reference genes. To further validate the stability of reference genes, the expression levels of two CYCD3 genes (BjuB045330 and BjuA003219) were studied. In addition, all genes in the xyloglucan endotransglucosylase/hydrolase (XTH) family were identified in B. juncea and their patterns at different periods of stem enlargement were analyzed. Results indicated that UBC and TUB genes showed stable levels of expression and are recommended for future research. In addition, XTH genes were involved in regulation of stem enlargement expression. These results provide new insights for future research aiming at exploring important functional genes, their expression patterns and regulatory mechanisms for mustard development.

scholarly journals What functional genomics has taught us about transcriptional regulation in malaria parasites

2019 ◽  
Vol 18 (5) ◽  
pp. 290-301 ◽  
Author(s):  
Christa G Toenhake ◽  
Richárd Bártfai
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Life Cycle ◽  
Functional Genomics ◽  
Expression Patterns ◽  
Regulatory Elements ◽  
Complex Life Cycle ◽  
Malaria Parasites ◽  
Gene Regulatory

Abstract Malaria parasites are characterized by a complex life cycle that is accompanied by dynamic gene expression patterns. The factors and mechanisms that regulate gene expression in these parasites have been searched for even before the advent of next generation sequencing technologies. Functional genomics approaches have substantially boosted this area of research and have yielded significant insights into the interplay between epigenetic, transcriptional and post-transcriptional mechanisms. Recently, considerable progress has been made in identifying sequence-specific transcription factors and DNA-encoded regulatory elements. Here, we review the insights obtained from these efforts including the characterization of core promoters, the involvement of sequence-specific transcription factors in life cycle progression and the mapping of gene regulatory elements. Furthermore, we discuss recent developments in the field of functional genomics and how they might contribute to further characterization of this complex gene regulatory network.

scholarly journals Correction to: Genetic variant predictors of gene expression provide new insight into risk of colorectal cancer

2019 ◽  
Vol 138 (7) ◽  
pp. 789-791
Author(s):  
Stephanie A. Bien ◽  
Yu-Ru Su ◽  
David V. Conti ◽  
Tabitha A. Harrison ◽  
Conghui Qu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Genetic Variant ◽  
Insight Into

Correlation of messenger RNA expression patterns of ERCC1, TS, EGFR, and VEGFR2 with KRAS and BRAF mutational status in advanced colorectal cancer: Implications for targeted therapies.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 383-383
Author(s):  
Martin K. H. Maus ◽  
Craig Stephens ◽  
Stephanie H. Astrow ◽  
Peter Philipp Grimminger ◽  
Dongyun Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Mrna Expression ◽  
Advanced Colorectal Cancer ◽  
Expression Patterns ◽  
Mrna Levels ◽  
Expression Levels ◽  
Mutational Status ◽  
Mrna Expression Levels ◽  
Gene Expression Levels

383 Background: Gene expression levels of ERCC1, TS, EGFR and VEGFR2 may have predictive value for the personalized use of standard chemotherapeutics as well as agents targeting the EGFR and VEGF pathways and the efficacy of EGFR directed monoclonal antibodies like panitumumab and cetuximab has been confirmed to be dependent on wt KRAS and wt BRAF in patients with advanced colorectal cancer. We investigated the correlations between KRAS/BRAF mutational status and the mRNA expression levels of these genes. Methods: Formalin-fixed paraffin-embedded tumor specimens from 600 patients with advanced colorectal adenocarcinoma were microdissected and DNA and RNA was extracted. Specifically designed primers and probes were used to detect 7 different base substitutions in codon 12 and 13 of KRAS, V600E mutations in BRAF and the expression levels of ERCC1, TS, EGFR and VEGFR2 by RT-PCR. Results: Mt KRAS tumors had significantly lower TS and EGFR gene expression levels compared with wt KRAS (p<0,001), whereas mt BRAF tumors showed significantly increased TS and EGFR mRNA levels compared to wt BRAF (p<0,001). Mt BRAF tumors showed significantly higher mRNA levels than mt KRAS tumors (p<0,001). ERCC1 and VEGFR2 mRNA levels were significantly down-regulated in mt KRAS specimen (p<0,001), but showed no significant correlation with BRAF mutational status. Conclusions: KRAS and BRAF mutations are associated with opposite mRNA expression levels for TS and EGFR. Recently, resistance to BRAF inhibition in mt BRAF colorectal tumors has been shown in preclinical models to be associated with up-regulation of EGFR. Our data suggests that BRAF mutants are associated with high EGFR levels at the time of diagnosis, and not necessarily part of an acquired mechanism of resistance. Significantly lower mRNA expression levels of VEGFR2 in mt KRAS tumors may explain lower response to angiogenesis inhibition seen in the TML study.

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