scholarly journals The crucial roles of N6-methyladenosine (m6A) modification in the carcinogenesis and progression of colorectal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhihao Fang ◽  
Yiqiu Hu ◽  
Jinhui Hu ◽  
Yanqin Huang ◽  
Shu Zheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Nuclear Export ◽  
Messenger Rna ◽  
Regulatory Proteins ◽  
Biological Processes ◽  
The Past ◽  
Common Cancer ◽  
Potential Applications ◽  
Regulated Gene Expression

AbstractAs the predominant modification in RNA, N6-methyladenosine (m6A) has attracted increasing attention in the past few years since it plays vital roles in many biological processes. This chemical modification is dynamic, reversible and regulated by several methyltransferases, demethylases and proteins that recognize m6A modification. M6A modification exists in messenger RNA and affects their splicing, nuclear export, stability, decay, and translation, thereby modulating gene expression. Besides, the existence of m6A in noncoding RNAs (ncRNAs) could also directly or indirectly regulated gene expression. Colorectal cancer (CRC) is a common cancer around the world and of high mortality. Increasing evidence have shown that the changes of m6A level and the dysregulation of m6A regulatory proteins have been implicated in CRC carcinogenesis and progression. However, the underlying regulation laws of m6A modification to CRC remain elusive and better understanding of these mechanisms will benefit the diagnosis and therapy. In the present review, the latest studies about the dysregulation of m6A and its regulators in CRC have been summarized. We will focus on the crucial roles of m6A modification in the carcinogenesis and development of CRC. Moreover, we will also discuss the potential applications of m6A modification in CRC diagnosis and therapeutics.

Human Platelet-Derived Factors Regulate Mesenchymal Stem Cell Gene Expression.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4255-4255
Author(s):  
Christina Malischnik ◽  
Katharina Schallmoser ◽  
Eva Rohde ◽  
Andreas Reinisch ◽  
Christian Guelly ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Growth Factors ◽  
Human Platelet ◽  
Ex Vivo ◽  
Expression Profiles ◽  
Cell Structure ◽  
Considerable Proportion ◽  
Biological Processes ◽  
Regulated Gene Expression

Abstract The use of animal-derived products during human stem cell processing bears the evident risk of xenogeneic prion, virus, or zoonose contamination. Human platelet lysate (HPL) has recently been recognized as a rich source of cytokines and growth factors with the potential to replace fetal bovine serum (FBS) during ex vivo stem cell manipulation. In this study we compared the gene expression profile of human multipotent mesenchymal stromal/stem cells (MSC) during ex vivo expansion for clinical applications under the aegis of either FBS or HPL. The Applied Biosystems 1700 Expression Array System was used for full genome expression profiling of MSC after a 12–14 day expansion period in a previously optimized low density expansion system. Data have been obtained from biological as well as technical replicates. A starting amount of 40μg total RNA was directly labeled and DIG-labeled cDNA was hybridized to Human Genome Survey Microarray V2.0. Attribution of regulated genes to biological processes and pathways was done using the PANTHER® db analysis software. We identified more than 300 genes that are differentially regulated upon culture of MSC in HPL compared to FBS. Biological processes specifically activated in HPL culture include mesoderm development, cell cycle control, hematopoiesis and angiogenesis which interestingly correspond to a considerable proportion of the regenerative function of MSC. In contrast, processes related to cell adhesion and adhesion-mediated signaling, cell structure, cell motility and cell communication are significantly upregulated in MSC after FBS in comparison to HPL culture. Replacing FBS with HPL not only avoids bovine prion, viral and zoonose contamination of MSC for clinical use. The tightly regulated gene expression profiles under the aegis of human growth factors and cytokines provided by HPL may even help to develop new stem cell therapy strategies.

Prognostic signatures of oligometastasis in colorectal cancer liver metastasis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3588-3588
Author(s):  
Sajid A. Khan ◽  
Philip Paty ◽  
Zhaoshi Zeng ◽  
Jun Lu
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Gene Family ◽  
Messenger Rna ◽  
Molecular Subtype ◽  
Prognostic Information ◽  
Hoxa Cluster ◽  
Hox Gene ◽  
Colorectal Cancer Liver Metastasis

3588 Background: Knowledge of molecular differences between limited metastasis (oligometastasis) and widespread metastases may provide biomarkers for selection of patients who will benefit from curative metastasis resection and provide useful prognostic information. In this study, we detect messenger RNA expressional patterns in patients with colorectal cancer liver metastasis (CRCLM) and identify networks of coding and noncoding RNAs corresponding to oligometastatic phenotype. Methods: RNA was prepared from frozen tumor tissue of 55 patients with CRCLM patients treated with liver resection and/or biopsy of their metastatic tumors with greater than 15 years of follow-up. Survival was calculated and stratified according to risk of recurrence. Cases were subject to RNA-Sequencing experiments with paired end sequencing. Results: RNA analysis with TopHat and Cuffdiff found significant differences in transcript expression according to recurrence for 667 genes (P < 0.05). Of these transcripts, 166 had a greater than 2-fold gene expression between groups when comparing mean Fragments Per Kilobase of transcript per Million mapped reads (FPKM) (P < 0.05). Unsupervised hierarchical clustering revealed distinct genomic patterns based on clinical outcome. A supervised gene expression analysis revealed a differential expression of genes in the Homeobox ( HOX) family (P < 0.05). Overexpression of individual members of the HOX gene family are associated with prognosis. Upregulation of the HOXD11 gene was associated with cure in 60% of cases while downregulation was associated with 5-year overall survivals of 16% (P = 0.023). Furthermore, when clusters of HOX family members were compared, we found that expression correlated with survival, underlining the importance of this gene family in oligometastasis biology. A high ratio of the HOXD cluster to HOXA cluster was associated with a long recurrence free survival (P = 0.002). Conclusions: Common genomic signatures characterize patients with liver oligometastasis from primary colorectal cancer. The HOX gene family strongly correlates with prognosis and represents a unique molecular subtype of patients. Further mechanistic studies of the HOX gene family in metastases are underway.

scholarly journals Regulation of mRNA cap methylation

2009 ◽  
Vol 425 (2) ◽  
pp. 295-302 ◽  
Author(s):  
Victoria H. Cowling
Keyword(s):  
Gene Expression ◽  
Cell Viability ◽  
Nuclear Export ◽  
Present Review ◽  
Biological Processes ◽  
Experimental Systems ◽  
Efficient Gene ◽  
Cellular Mrnas ◽  
Eukaryotic Organisms ◽  
The Impact

The 7-methylguanosine cap added to the 5′ end of mRNA is essential for efficient gene expression and cell viability. Methylation of the guanosine cap is necessary for the translation of most cellular mRNAs in all eukaryotic organisms in which it has been investigated. In some experimental systems, cap methylation has also been demonstrated to promote transcription, splicing, polyadenylation and nuclear export of mRNA. The present review discusses how the 7-methylguanosine cap is synthesized by cellular enzymes, the impact that the 7-methylguanosine cap has on biological processes, and how the mRNA cap methylation reaction is regulated.

scholarly journals CDK8 and CDK19 kinases have non-redundant oncogenic functions in hepatocellular carcinoma

2019 ◽  
Author(s):  
Katarina Bacevic ◽  
Susana Prieto ◽  
Stefano Caruso ◽  
Alain Camasses ◽  
Geronimo Dubra ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Hepatocellular Carcinoma ◽  
Poor Prognosis ◽  
Kinase Inhibitor ◽  
Advanced Disease ◽  
Chemical Carcinogenesis ◽  
Liver Carcinogenesis ◽  
Common Cancer ◽  
Genetic Deletion

AbstractHepatocellular carcinoma (HCC) is a common cancer with high mortality. The limited therapeutic options for advanced disease include treatment with Sorafenib, a multi-kinase inhibitor whose targets include the Mediator kinase CDK8. Since CDK8 has reported oncogenic activity in Wnt-dependent colorectal cancer, we investigated whether it is also involved in HCC. We find that CDK8 and its paralogue CDK19 are significantly overexpressed in HCC patients, where high levels correlate with poor prognosis. Liver-specific genetic deletion of CDK8 in mice is well supported and protects against chemical carcinogenesis. Deletion of either CDK8 or CDK19 in hepatic precursors had little effect on gene expression in exponential cell growth but prevented oncogene-induced transformation. This phenotype was reversed by concomitant deletion of TP53. These data support important and non-redundant roles for mediator kinases in liver carcinogenesis, where they genetically interact with the TP53 tumor suppressor.

Epigenetically regulated gene expression profiles reveal four molecular subtypes with prognostic and therapeutic implications in colorectal cancer

2020 ◽  
Author(s):  
Xiaokang Wang ◽  
Jinfeng Liu ◽  
Danwen Wang ◽  
Maohui Feng ◽  
Xiongzhi Wu
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Metabolic Activity ◽  
Poor Prognosis ◽  
Molecular Subtypes ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Epigenetic Mechanisms ◽  
Regulated Gene Expression ◽  
Marked Proliferation

Abstract Transcriptomic deregulation by epigenetic mechanisms plays a crucial role in the heterogeneous progression of colorectal cancer (CRC). Herein, we first demonstrated that the frequencies of the aberrancies of DNA methylation-correlated (METcor) and microRNA (miRNA)-correlated (MIRcor) genes were significantly co-regulated. Next, through integrative clustering of the expression profiles of METcor and MIRcor genes, four molecular subtypes were identified in CRC patients from The Cancer Genome Atlas and then validated in four independent datasets. More importantly, the four subtypes were well characterized and showed distinct clinical and molecular features: (i) S-I: high metabolic activity, sensitive to 5-fluorouracil-based chemotherapy and good prognosis; (ii) S-II: moderate metabolic activity, marked proliferation, frequent KRAS mutation and intermediate prognosis; (iii) S-III: moderate metabolic activity, marked proliferation, promoter DNA hypermethylation, high mutation burden, frequent BRAF and EGFR mutations, moderate levels of epithelial-mesenchymal transition (EMT) and transforming growth factor β (TGFβ) signals, immune-inflamed phenotype, sensitive to cetuximab and death protein-1 inhibitor treatment and relatively poor prognosis and (iv) S-IV: miRNA overexpression, stem/serrated/mesenchymal-like properties, hypoxia, high levels of EMT and TGFβ signals, immune-excluded phenotype and poor prognosis. Overall, this study established a molecular classification based on epigenetically regulated gene expression profiles, thereby providing a better understanding of the epigenetic mechanisms underlying CRC heterogeneity.

MicroRNAs for Diagnosis and Treatment of Colorectal Cancer

2020 ◽  
Vol 20 ◽  
Author(s):  
Haitao Mei ◽  
Yugang Wen
Keyword(s):  
Colorectal Cancer ◽  
Disease Free Survival ◽  
Diagnosis And Treatment ◽  
High Morbidity ◽  
Circulating Micrornas ◽  
Free Survival ◽  
The Past ◽  
Common Cancer ◽  
Disease Free

: Colorectal cancer (CRC) is the third most common cancer worldwide, with high morbidity and mortality rates. The diagnosis and treatment of CRC have the most significant value for disease-free survival. Early diagnosis and early surgical resection are generally considered to be the most effective ways to reduce CRC mortality. In the past few years, many researchers have focused on the role of microRNAs in different tumors, making the functions of microRNAs gradually clear. The present study reviews the role of microRNAs in the diagnosis and treatment of colorectal cancer. Compared with the usual diagnosis methods and biomarker, circulating microRNAs can be promising new effective biomarkers for CRCdiagnosis and treatment.

scholarly journals Methylation and Gene Expression of BCAT1 and IKZF1 in Colorectal Cancer Tissues

2018 ◽  
Vol 12 ◽  
pp. 117955491877506 ◽  
Author(s):  
Maher Jedi ◽  
Graeme P Young ◽  
Susanne K Pedersen ◽  
Erin L Symonds
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Messenger Rna ◽  
Stage Iv ◽  
Mrna Levels ◽  
Polymerase Chain ◽  
Cancer Tissues ◽  
The Relationship ◽  
Neoplastic Tissues

The genes BCAT1 and IKZF1 are hypermethylated in colorectal cancer (CRC), but little is known about how this relates to gene expression. This study assessed the relationship between methylation and gene expression of BCAT1 and IKZF1 in CRC and adjacent non-neoplastic tissues. The tissues were obtained at surgery from 36 patients diagnosed with different stages of CRC (stage I n = 8, stage II n = 13, stage III n = 10, stage IV n = 5). Methylated BCAT1 and IKZF1 were detected in 92% and 72% CRC tissues, respectively, with levels independent of stage ( P > .05). In contrast, only 31% and 3% of non-neoplastic tissues were methylated for BCAT1 and IKZF1, respectively ( P < .001). The IKZF1 messenger RNA (mRNA) expression was significantly lower in the cancer tissues compared with that of non-neoplastic tissues, whereas the BCAT1 mRNA levels were similar. The latter may be due to the BCAT1 polymerase chain reaction assay detecting more than 1 mRNA transcript. Further studies are warranted to establish the role of the epigenetic silencing of IKZF1 in colorectal oncogenesis.

scholarly journals Nuclear Accumulation of the GATA Factor AreA in Response to Complete Nitrogen Starvation by Regulation of Nuclear Export

2005 ◽  
Vol 4 (10) ◽  
pp. 1646-1653 ◽  
Author(s):  
Richard B. Todd ◽  
James A. Fraser ◽  
Koon Ho Wong ◽  
Meryl A. Davis ◽  
Michael J. Hynes
Keyword(s):  
Gene Expression ◽  
Nitrogen Source ◽  
Nuclear Export ◽  
Nitrogen Starvation ◽  
Nitrogen Sources ◽  
Nuclear Accumulation ◽  
Gata Factor ◽  
Regulated Gene Expression ◽  
Activation Capacity

ABSTRACT Both the availability and the quality of nutrients affect cellular functions by controlling gene activity. AreA, a member of the GATA family of transcription factors, globally activates expression of genes involved in nitrogen source utilization in Aspergillus nidulans. The quality of the nitrogen source determines the level and activation capacity of AreA through controls at the level of areA mRNA stability and by interaction of AreA with the corepressor NmrA. The availability of potential nitrogen sources also affects the activation capacity of AreA. We show that the complete absence of a nitrogen source results in an enhanced level of AreA-dependent gene expression and that this response is independent of mechanisms regulating AreA activity in response to nitrogen source quality. During nitrogen starvation AreA accumulates in the nucleus, but the presence of a potential nitrogen source or carbon starvation prevents this accumulation. Furthermore, accumulated AreA is rapidly lost from the nuclei of nitrogen-starved cells when a nitrogen source is supplied or when a carbon source is absent, and this accompanies arrest of the AreA-dependent nitrogen starvation response on regulated gene expression. By the generation of a leptomycin B-sensitive mutant, we have been able to show that nuclear exit occurs via the CrmA exportin. We conclude that sensing mechanisms discriminate between starvation and the presence of potential nutrients that can signal to the AreA transcription factor. Nitrogen source availability, but not quality, affects nuclear accumulation by regulating nuclear exit of AreA, providing a rapid response to changes in the supply of nutrients.

scholarly journals Membraneless organelles: phasing out of equilibrium

2020 ◽  
Vol 4 (3) ◽  
pp. 343-354 ◽  
Author(s):  
Maria Hondele ◽  
Stephanie Heinrich ◽  
Paolo De Los Rios ◽  
Karsten Weis
Keyword(s):  
Gene Expression ◽  
Phase Separation ◽  
Biological Processes ◽  
Cellular Organization ◽  
Multiple Strategies ◽  
The Past ◽  
Equilibrium Process ◽  
And Control ◽  
Liquid Liquid Phase Separation ◽  
Non Equilibrium

Over the past years, liquid–liquid phase separation (LLPS) has emerged as a ubiquitous principle of cellular organization implicated in many biological processes ranging from gene expression to cell division. The formation of biological condensates, like the nucleolus or stress granules, by LLPS is at its core a thermodynamic equilibrium process. However, life does not operate at equilibrium, and cells have evolved multiple strategies to keep condensates in a non-equilibrium state. In this review, we discuss how these non-equilibrium drivers counteract solidification and potentially detrimental aggregation, and at the same time enable biological condensates to perform work and control the flux of substrates and information in a spatial and temporal manner.

Splicing of plant pre-mRNAs

1992 ◽  
Vol 99 (3-4) ◽  
pp. 31-50 ◽  
Author(s):  
Craig G. Simpson ◽  
Gordon G. Simpson ◽  
Gillian Clark ◽  
David J. Leader ◽  
Petra Vaux ◽  
...  
Keyword(s):  
Gene Expression ◽  
Messenger Rna ◽  
Genetic Manipulation ◽  
Mrna Splicing ◽  
Mrna Transcripts ◽  
Dicotyledonous Plants ◽  
Intron Recognition ◽  
The Difference ◽  
Biochemical Analyses ◽  
Regulated Gene Expression

SynopsisPre-messenger RNA (pre-mRNA) splicing or the removal of introns from pre-mRNA transcripts is a key process in the maturation of mRNA. This process requires the assembly of a large complex of RNA and protein molecules, called the splicosome, on the pre-mRNA transcripts. Molecular and biochemical analyses of plant intron sequence and structure and of the components of the plant spliceosome are providing information on the mechanism of intron recognition and splice site selection in both monocoty-ledonous and dicotyledonous plants. This knowledge will help in gaining an understanding of phenomena such as the difference in splicing between monocotyledonous and dictoyledonous plants, the enhancement of gene expression brought about by the presence of some introns and alternative splicing. The importance of introns and pre-mRNA splicing to accurate and regulated gene expression, therefore, is of direct relevance to transgene expression and genetic manipulation.

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