scholarly journals The Intricate Interplay between Epigenetic Events, Alternative Splicing and Noncoding RNA Deregulation in Colorectal Cancer

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 929 ◽  
Author(s):  
Raheleh Amirkhah ◽  
Hojjat Naderi-Meshkin ◽  
Jaynish Shah ◽  
Philip Dunne ◽  
Ulf Schmitz
Keyword(s):  
Colorectal Cancer ◽  
Alternative Splicing ◽  
Noncoding Rna ◽  
Tumour Microenvironment ◽  
Rna Regulation ◽  
Non Coding Rna ◽  
Epigenetic Events ◽  
Transcriptional Gene Regulation ◽  
Aberrant Dna Methylation ◽  
And Function

Colorectal cancer (CRC) results from a transformation of colonic epithelial cells into adenocarcinoma cells due to genetic and epigenetic instabilities, alongside remodelling of the surrounding stromal tumour microenvironment. Epithelial-specific epigenetic variations escorting this process include chromatin remodelling, histone modifications and aberrant DNA methylation, which influence gene expression, alternative splicing and function of non-coding RNA. In this review, we first highlight epigenetic modulators, modifiers and mediators in CRC, then we elaborate on causes and consequences of epigenetic alterations in CRC pathogenesis alongside an appraisal of the complex feedback mechanisms realized through alternative splicing and non-coding RNA regulation. An emphasis in our review is put on how this intricate network of epigenetic and post-transcriptional gene regulation evolves during the initiation, progression and metastasis formation in CRC.

scholarly journals Human Long Noncoding RNA Interactome: Detection, Characterization and Function

2020 ◽  
Vol 21 (3) ◽  
pp. 1027 ◽  
Author(s):  
Kazimierczyk ◽  
Kasprowicz ◽  
Kasprzyk ◽  
Wrzesinski
Keyword(s):  
Noncoding Rna ◽  
Potential Role ◽  
Integrated Analysis ◽  
Biological Functions ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
And Function ◽  
New Generation ◽  
Cellular Components ◽  
Proteins And Peptides

The application of a new generation of sequencing techniques has revealed that most of the genome has already been transcribed. However, only a small part of the genome codes proteins. The rest of the genome "dark matter” belongs to divergent groups of non-coding RNA (ncRNA), that is not translated into proteins. There are two groups of ncRNAs, which include small and long non-coding RNAs (sncRNA and lncRNA respectively). Over the last decade, there has been an increased interest in lncRNAs and their interaction with cellular components. In this review, we presented the newest information about the human lncRNA interactome. The term lncRNA interactome refers to cellular biomolecules, such as nucleic acids, proteins, and peptides that interact with lncRNA. The lncRNA interactome was characterized in the last decade, however, understanding what role the biomolecules associated with lncRNA play and the nature of these interactions will allow us to better understand lncRNA's biological functions in the cell. We also describe a set of methods currently used for the detection of lncRNA interactome components and the analysis of their interactions. We think that such a holistic and integrated analysis of the lncRNA interactome will help to better understand its potential role in the development of organisms and cancers.

scholarly journals Identification the role of mono-ADP-ribosylation in colorectal cancer by integrated Transcriptome analysis

2021 ◽  
Author(s):  
Shuxian Zhang ◽  
Jiale Duan ◽  
Yanping Yang ◽  
Hanjuan Gong ◽  
Yi Tang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Endoplasmic Reticulum ◽  
Alternative Splicing ◽  
Enrichment Analysis ◽  
Drug Candidate ◽  
Post Translational Modification ◽  
Lentiviral Infection ◽  
Whole Transcriptome Sequencing ◽  
And Function

Abstract Purpose Our previous study has clarified the carcinogenic properties of arginine-specific mono-ADP ribosyltransferase 1(ART1), which is considered to be a critical post-translational modification that changes the structure and function of proteins and is widely involved in important processes. This study provides, for the first time, a comprehensive insight of transcriptomic analysis for colorectal cancer cells interfered with ART1 silencing by Illumina RNA-Seq and related verification experiments. Methods Lentiviral infection was used to construct a CT-26 cell line that stably knocks down the ART1 gene, a whole transcriptome sequencing technique was performed to identify differentially expressed genes (DEGs). GO and KEGG classification/enrichment analysis and verification experiments were performed to determine the role of ART1 in the progression of colorectal cancer. Results a total of 5552 DEGs, GO function and KEGG pathway with highest enrichment, forms of SNP and diverse splicing patterns were able to be identified. Importantly, knockdown of ART1 affected the occurrence of the splicing of certain key genes related to tumor cell growth, also down-regulated expression of the key gene PTBP1 for alternative splicing. The overall attenuation of the endoplasmic reticulum unfolded protein response (UPR) signaling pathway caused by ART1 inhibition would unbalance UPR signaling, leading to the occurrence of apoptosis to impede tumorigenesis. Conclusion ART1, which clustered in organelles, may promote the development of colorectal cancer by participating in a variety of new mechanisms including endoplasmic reticulum stress regulation, metabolic process or alternative splicing, which may provide a good clinical drug candidate closer to targeted therapy of CRC.

scholarly journals Mechanisms of Long Non-Coding RNAs in Cancers and Their Dynamic Regulations

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1245 ◽  
Author(s):  
Xiao-Zhen Zhang ◽  
Hao Liu ◽  
Su-Ren Chen
Keyword(s):  
Noncoding Rna ◽  
Translational Regulation ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Cancer Therapies ◽  
Search Terms ◽  
Non Coding Rna ◽  
Pubmed Database ◽  
And Function ◽  
Long Non Coding Rna

Long non-coding RNA (lncRNA), which is a kind of noncoding RNA, is generally characterized as being more than 200 nucleotide transcripts in length. LncRNAs exhibit many biological activities, including, but not limited to, cancer development. In this review, a search of the PubMed database was performed to identify relevant studies published in English. The term “lncRNA or long non-coding RNA” was combined with a range of search terms related to the core focus of the review: mechanism, structure, regulation, and cancer. The eligibility of the retrieved studies was mainly based on the abstract. The decision as to whether or not the study was included in this review was made after a careful assessment of its content. The reference lists were also checked to identify any other study that could be relevant to this review. We first summarized the molecular mechanisms of lncRNAs in tumorigenesis, including competing endogenous RNA (ceRNA) mechanisms, epigenetic regulation, decoy and scaffold mechanisms, mRNA and protein stability regulation, transcriptional and translational regulation, miRNA processing regulation, and the architectural role of lncRNAs, which will help a broad audience better understand how lncRNAs work in cancer. Second, we introduced recent studies to elucidate the structure of lncRNAs, as there is a link between lncRNA structure and function and visualizing the architectural domains of lncRNAs is vital to understanding their function. Third, we explored emerging evidence for regulators of lncRNA expression, lncRNA turnover, and lncRNA modifications (including 5-methylcytidine, N6-methyladenosine, and adenosine to inosine editing), highlighting the dynamics of lncRNAs. Finally, we used autophagy in cancer as an example to interpret the diverse mechanisms of lncRNAs and introduced clinical trials of lncRNA-based cancer therapies.

scholarly journals A genomic screen for long noncoding RNA genes epigenetically silenced by aberrant DNA methylation in colorectal cancer

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Kohei Kumegawa ◽  
Reo Maruyama ◽  
Eiichiro Yamamoto ◽  
Masami Ashida ◽  
Hiroshi Kitajima ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Genomic Screen ◽  
Aberrant Dna Methylation ◽  
Rna Genes

scholarly journals Complete Transcriptome Profiling of Normal and Age-Related Macular Degeneration Eye Tissues Reveals Changes in Regulation of Non-Coding RNA and Extreme Disregulation of Anti-Sense Transcription

2017 ◽  
Author(s):  
Eun Ji Kim ◽  
Gregory G. Grant ◽  
Anita S. Bowman ◽  
Naqi Haider ◽  
Harini V. Gudiseva ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Noncoding Rna ◽  
Transcriptome Profiling ◽  
Age Related Macular Degeneration ◽  
Rna Regulation ◽  
Normal Retina ◽  
Age Related ◽  
Non Coding Rna ◽  
Eye Tissues ◽  
High Level

AbstractStrand specific RNA sequencing of retina and RPE-Choroid-Scleara (RCS) in age-related macular degeneration (AMD) and matched normal controls reveals striking impact on anti-sense transcription and changes in the regulation of non-coding RNA that has not previously been reported. Hundreds of genes, which do not express anti-sense transcripts in normal retina and RCS, demonstrate extreme anti-sense expression in AMD. And conversely anti-sense transcription is completely abrogated in many genes which express a high level of anti-sense transcripts in normal retina and RCS. Several pathways are very highly enriched in the upregulated anti-sense transcripts - in particular the EIF2 signaling pathway. These results call for a deeper investigation into anti-sense and noncoding RNA regulation in AMD and their potential as therapeutic targets.

scholarly journals The PVT1 lncRNA is a novel epigenetic enhancer of MYC, and a promising risk-stratification biomarker in colorectal cancer

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Kunitoshi Shigeyasu ◽  
Shusuke Toden ◽  
Tsuyoshi Ozawa ◽  
Takatoshi Matsuyama ◽  
Takeshi Nagasaka ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Aberrant Methylation ◽  
Enhancer Activity ◽  
Transcriptional Enhancers ◽  
Cancer Pathogenesis ◽  
Non Coding Rna ◽  
Genome Wide ◽  
A Genome ◽  
And Function ◽  
Long Non Coding Rna

Abstract Accumulating evidence suggests that dysregulation of transcriptional enhancers plays a significant role in cancer pathogenesis. Herein, we performed a genome-wide discovery of enhancer elements in colorectal cancer (CRC). We identified PVT1 locus as a previously unrecognized transcriptional regulator in CRC with a significantly high enhancer activity, which ultimately was responsible for regulating the expression of MYC oncogene. High expression of the PVT1 long-non-coding RNA (lncRNA) transcribed from the PVT1 locus was associated with poor survival among patients with stage II and III CRCs (p < 0.05). Aberrant methylation of the PVT1 locus inversely correlated with the reduced expression of the corresponding the PVT1 lncRNA, as well as MYC gene expression. Bioinformatic analyses of CRC-transcriptomes revealed that the PVT1 locus may also broadly impact the expression and function of other key genes within two key CRC-associated signaling pathways – the TGFβ/SMAD and Wnt/β-Catenin pathways. We conclude that the PVT1 is a novel oncogenic enhancer of MYC and its activity is controlled through epigenetic regulation mediated through aberrant methylation in CRC. Our findings also suggest that the PVT1 lncRNA expression is a promising prognostic biomarker and a potential therapeutic target in CRC.

scholarly journals Four novel polymorphisms in long non-coding RNA HOTTIP are associated with the risk and prognosis of colorectal cancer

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Zhi Lv ◽  
Qian Xu ◽  
Liping Sun ◽  
Jing Wen ◽  
Xinxin Fang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Susceptibility ◽  
Human Cancer ◽  
Predictive Biomarkers ◽  
Nucleotide Polymorphisms ◽  
Specific Pcr ◽  
Non Coding Rna ◽  
And Function ◽  
Stratified Analysis ◽  
Long Non Coding Rna

AbstractBackground: The role of long non-coding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) as an oncogene in varieties of human cancer including colorectal cancer (CRC) has been extensively researched. The expression and function of lncRNAs could be affected by single nucleotide polymorphisms (SNPs), which are associated with cancer susceptibility and prognosis. However, no investigation has focused on the association between HOTTIP SNPs and CRC. The aim of the present study was to explore the association of polymorphisms in the lncRNA HOTTIP gene with CRC risk and prognosis. Methods: A total of 1848 subjects were enrolled in our study, including 884 CRC cases and 964 controls. Genotyping for five HOTTIP tagSNPs (rs3807598, rs17501292, rs2067087, rs17427960, and rs78248039) was performed by applying Kompetitive allele specific PCR (KASP). Results: The results showed three SNPs (rs3807598, rs2067087, and rs17427960) were associated with enhanced CRC risk both in overall and stratified analysis. One polymorphism, rs17501292, could improve the overall survival (OS) of CRC patients in the tumor of ulcerative/invasive-type subgroup. Conclusion: These findings suggest HOTTIP SNPs could potentially be predictive biomarkers for CRC risk and prognosis. The present study provides clues for further exploration of novel lncRNA-based genetic biomarkers to predict CRC susceptibility as well as clinical outcome.

scholarly journals Natural Antisense Transcript PEBP1P3 Regulates the RNA Expression, DNA Methylation and Histone Modification of CD45 Gene

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 759
Author(s):  
Zhongjing Su ◽  
Guangyu Liu ◽  
Bin Zhang ◽  
Ze Lin ◽  
Dongyang Huang
Keyword(s):  
Dna Methylation ◽  
Alternative Splicing ◽  
Histone Modification ◽  
Antisense Rna ◽  
Noncoding Rna ◽  
Antisense Transcript ◽  
Natural Antisense Transcript ◽  
Regulation Of Expression ◽  
Splicing Isoforms ◽  
Intron 2

The leukocyte common antigen CD45 is a transmembrane phosphatase expressed on all nucleated hemopoietic cells, and the expression levels of its splicing isoforms are closely related to the development and function of lymphocytes. PEBP1P3 is a natural antisense transcript from the opposite strand of CD45 intron 2 and is predicted to be a noncoding RNA. The genotype-tissue expression and quantitative PCR data suggested that PEBP1P3 might be involved in the regulation of expression of CD45 splicing isoforms. To explore the regulatory mechanism of PEBP1P3 in CD45 expression, DNA methylation and histone modification were detected by bisulfate sequencing PCR and chromatin immunoprecipitation assays, respectively. The results showed that after the antisense RNA PEBP1P3 was knocked down by RNA interference, the DNA methylation of CD45 intron 2 was decreased and histone H3K9 and H3K36 trimethylation at the alternative splicing exons of CD45 DNA was increased. Knockdown of PEBP1P3 also increased the binding levels of chromatin conformation organizer CTCF at intron 2 and the alternative splicing exons of CD45. The present results indicate that the natural antisense RNA PEBP1P3 regulated the alternative splicing of CD45 RNA, and that might be correlated with the regulation of histone modification and DNA methylation.

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