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Molecular Therapy. Nucleic Acids Jun 2020N4-acetylcytidine (ac4C) is often considered to be a conservative, chemically modified nucleoside present on tRNA and rRNA. Recent studies have shown extensive ac4C... (Review)
Review
N4-acetylcytidine (ac4C) is often considered to be a conservative, chemically modified nucleoside present on tRNA and rRNA. Recent studies have shown extensive ac4C modifications in human and yeast mRNAs. ac4C helps to correctly read codons during translation and improves translation efficiency and the stability of mRNA. At present, the research of ac4C involves a variety of detection methods. The formation of ac4C is closely related to N-acetyltransferase 10 (NAT10) and its helpers, such as putative tRNA acetyltransferase (TAN1) for tRNA ac4C and small nucleolar RNA (snoRNA) for rRNA ac4C. Also, ac4C is associated with the development, progression, and prognosis of a variety of human diseases. Here, we summarize the history of ac4C research and the detection technologies of ac4C. We then summarized the role and mechanism of ac4C in gene-expression regulation and demonstrated the relevance of ac4C to a variety of human diseases, especially cancer. Finally, we list the future challenges of the ac4C research and demonstrate a research strategy for the interactions among several abundant modified nucleosides on mRNA.
PubMed: 32171170
DOI: 10.1016/j.omtn.2020.01.037 -
Gene Mar 2020Gene expression is the process by which DNA is decoded to produce a functional transcript. The collection of all transcripts is referred to as the transcriptome and has... (Comparative Study)
Comparative Study
Gene expression is the process by which DNA is decoded to produce a functional transcript. The collection of all transcripts is referred to as the transcriptome and has extensively been used to evaluate differentially expressed genes in a certain cell or tissue type. In response to internal or external stimuli, the transcriptome is greatly regulated by epigenetic changes. Many studies have elucidated that antemortem gene expression (transcriptome) may be linked to an array of disease etiologies as well as potential targets for drug discovery; on the other hand, a number of studies have utilized postmortem gene expression (thanatotranscriptome) patterns to determine cause and time of death. The "transcriptome after death" involves the study of mRNA transcripts occurring in human tissues after death (thanatos, Greek for death). While antemortem gene expression can provide a wide range of important information about the host, the determination of the communication of genes after a human dies has recently been explored. After death a plethora of genes are regulated via activation versus repression as well as diverse regulatory factors such as the absence or presence of stimulated feedback. Even postmortem transcriptional regulation contains many more cellular constituents and is massively more complicated. The rates of degradation of mRNA transcripts vary depending on the types of postmortem tissues and their combinatorial gene expression signatures. mRNA molecules have been shown to persist for extended time frames; nevertheless, they are highly susceptible to degradation, with half-lives of selected mRNAs varying between minutes to weeks for specifically induced genes. Furthermore, postmortem genetic studies may be used to improve organ transplantation techniques. This review is the first of its kind to fully explore both gene expression and mRNA stability after death and the trove of information that can be provided about phenotypical characteristics of specific genes postmortem.
Topics: Animals; Autopsy; Death; Gene Expression Profiling; Gene Expression Regulation; Humans; Life; Life Style; Postmortem Changes; RNA Stability; RNA, Messenger; Transcriptome
PubMed: 31935499
DOI: 10.1016/j.gene.2020.144349 -
Artificial Cells, Nanomedicine, and... Dec 2020OIP5-AS1 has been reported to be aberrantly expressed in multiple cancers and associated with clinical outcomes. We conducted this study to assess the generalized...
OIP5-AS1 has been reported to be aberrantly expressed in multiple cancers and associated with clinical outcomes. We conducted this study to assess the generalized prognostic value of OIP5-AS1 in cancers. PubMed, Web of science, and Cochrane Library were searched for eligible studies. Hazards ratios (HRs) or odd ratios (ORs) with 95% confidence intervals (CIs) were pooled to estimate the prognostic value of OIP5-AS1 in cancers, including overall survival (OS), age, gender, tumor size, clinical stage, and lymph node metastasis (LNM). Publication bias was measured by Begg's test and funnel plot. Sensitivity analysis were used to detect the stability of pooled results. Overall, eleven studies containing 713 patients were eventually enrolled. The pooled results showed that high OIP5-AS1 expression was correlated with shorter OS (HR = 0.48, 95%CI: 0.35-0.64), regardless of the sample size, tumor type and follow-up time. Furthermore, elevated expression of OIP5-AS1 indicated advanced clinical stage (OR = 2.12, 95% CI: 1.06-4.23), but not associated with age, gender, tumor size and LNM. No publication bias was detected. High expression of lncRNA OIP5-AS1 may predict a poor OS and advanced clinical stage, implicating that OIP5-AS1 may be a possible prognostic factor in cancers.
Topics: Disease-Free Survival; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Neoplasm Staging; Neoplasms; RNA, Long Noncoding; RNA, Neoplasm; Survival Rate
PubMed: 31899963
DOI: 10.1080/21691401.2019.1709854 -
Epigenomics Jan 2020Despite remarkable improvements in survival of childhood acute lymphoblastic leukemia (ALL), nonresponding or relapsing patients still represent one of the most frequent...
Despite remarkable improvements in survival of childhood acute lymphoblastic leukemia (ALL), nonresponding or relapsing patients still represent one of the most frequent causes of death by disease in children. Accurate patient risk stratification based on genetic markers could increases survival rates. miRNAs can represent novel candidates with diagnostic, predictive and prognostic potential; however, many groups investigated their involvement with contradictory results. To clarify the role of miRNAs as biomarkers through a systematic review. From a revision of 45 manuscripts, we found that miR-128 and miR-181 overexpression could represent markers for ALL diagnosis and underexpression of miR-708 and miR-99a could be markers for bad prognosis. These signatures could refine classification and risk stratification of patients and improve ALL outcome.
Topics: Biomarkers, Tumor; Disease Susceptibility; Gene Expression Profiling; Gene Expression Regulation, Leukemic; Humans; MicroRNAs; Precursor Cell Lymphoblastic Leukemia-Lymphoma; RNA Stability
PubMed: 31833405
DOI: 10.2217/epi-2019-0154 -
Pathology, Research and Practice Dec 2019Mounting studies has revealed that circular RNAs (circRNAs) play a key role in tumorigenesis and might serve as promising biomarkers for cancer diagnosis. However, the... (Meta-Analysis)
Meta-Analysis
PURPOSE
Mounting studies has revealed that circular RNAs (circRNAs) play a key role in tumorigenesis and might serve as promising biomarkers for cancer diagnosis. However, the diagnostic value of circRNAs in colorectal cancer (CRC) remains to be precisely elucidated.
METHODS
All relevant literatures were searched using Cochrane Library, PubMed, Web of Science, EMBASE, CNKI, and WanFang databases up to June 2019. The quality of eligible studies was assessed in accordance with the Quality Assessment of Diagnostic Accuracy Studies-2 system. The summary receiver operator characteristic curve (SROC) and area under SROC (AUC) were applied for the quantitative assessment of diagnostic performance. Threshold effect, subgroup analysis, and meta-regression were adopted to explore the sources of heterogeneity. Deeks' funnel plot and sensitivity analysis were conducted to examine the publication bias and stability of meta-analysis, respectively.
RESULTS
A total of 13 eligible studies involving 2190 subjects and 14 different kinds of circRNAs were enrolled. The pooled sensitivity, specificity, and AUC were 0.78 [95% confidential interval (CI): 0.70-0.84], 0.71 (95% CI: 0.65-0.76), and 0.80 (95% CI: 0.76-0.83), respectively. Subgroup analysis showed that studies involving ≥ 100 cases had higher sensitivity but lower specificity than those involving < 100 cases. Meta-regression revealed that sample size might be the potential source of heterogeneity. Sensitivity analysis and Deeks' funnel plot indicated that our results were relatively robust and had no publication bias.
CONCLUSION
CircRNAs possess relatively moderate diagnostic accuracy and might serve as potential diagnostic biomarkers for colorectal cancer. Future large-scale studies are needed to confirm the diagnostic value of circRNAs.
Topics: Biomarkers, Tumor; Colorectal Neoplasms; Gene Expression Regulation, Neoplastic; Humans; Molecular Diagnostic Techniques; Predictive Value of Tests; Prognosis; RNA, Circular; RNA, Neoplasm; Reproducibility of Results
PubMed: 31635986
DOI: 10.1016/j.prp.2019.152680 -
International Journal of Biological... 2019p53 is the major mediator of the tumor suppressor response. It participates in apoptosis and senescence and can respond to DNA damage. As a crucial sequence-specific...
p53 is the major mediator of the tumor suppressor response. It participates in apoptosis and senescence and can respond to DNA damage. As a crucial sequence-specific transcription factor, p53 regulates the expression of many genes, such as small noncoding RNAs (ncRNAs), microRNAs, and long ncRNAs (lncRNAs). Given the emergence of novel and high-throughput sequencing technologies, many lncRNAs have been discovered. LncRNAs may function as vital gene regulators in a variety of biological processes through extensive mechanisms. Recently, lncRNAs have been demonstrated to be associated with the p53 regulatory pathway. In this review, we discuss the current and fast growing knowledge about the influence of lncRNAs to the p53 signaling pathway, the different mechanisms by which they affect gene expression in cancer. Our findings show that p53-associated lncRNAs may be used as biomarkers for cancer diagnosis or targets for disease therapy.
Topics: Cell Proliferation; Disease Progression; Humans; Neoplasms; Protein Processing, Post-Translational; Protein Stability; RNA, Long Noncoding; Signal Transduction; Tumor Suppressor Protein p53
PubMed: 31223287
DOI: 10.7150/ijbs.33218 -
Frontiers in Physiology 2019The pentatricopeptide repeat (PPR) family plays a major role in RNA stability, regulation, processing, splicing, translation, and editing. Leucine-rich...
The pentatricopeptide repeat (PPR) family plays a major role in RNA stability, regulation, processing, splicing, translation, and editing. Leucine-rich PPR-motif-containing protein (LRPPRC), a member of the PPR family, is a known gene mutation that causes Leigh syndrome French-Canadian. Recently, growing evidence has pointed out that LRPPRC dysregulation is related to various diseases ranging from tumors to viral infections. This review presents available published data on the LRPPRC protein function and its role in tumors and other diseases. As a multi-functional protein, LRPPRC regulates a myriad of biological processes, including energy metabolism and maturation and the export of nuclear mRNA. Overexpression of LRPPRC has been observed in various human tumors and is associated with poor prognosis. Downregulation of LRPPRC inhibits growth and invasion, induces apoptosis, and overcomes drug resistance in tumor cells. In addition, LRPPRC plays a potential role in Parkinson's disease, neurofibromatosis 1, viral infections, and venous thromboembolism. Further investigating these new functions of LRPPRC should provide novel opportunities for a better understanding of its pathological role in diseases from tumors to viral infections and as a potential biomarker and molecular target for disease treatment.
PubMed: 31178748
DOI: 10.3389/fphys.2019.00595 -
Journal of Cellular Physiology May 2019MicroRNAs (miRNAs) are an important class of endogenous small noncoding single-stranded RNAs that suppress the expression of their target genes through messenger RNA...
MicroRNAs (miRNAs) are an important class of endogenous small noncoding single-stranded RNAs that suppress the expression of their target genes through messenger RNA (mRNA) degradation to inhibit transcription and translation. MiRNAs play a crucial regulatory role in many biological processes including proliferation, metabolism, and cellular malignancy. miR-15a/16 is an important tumor suppressor gene cluster with a variety of factors that regulate its transcriptional activity. It has been discovered that a relative reduction of miR-15a/16 expression in various cancers is closely related to the occurrence and progression of tumors. miR-15a/16 takes part in a wide array of biological processes including tumor cell proliferation, apoptosis, invasion, and chemoresistance by binding to the 3'-untranslated region of its target gene's mRNA. In this review, we will examine the complex regulatory network of miR-15a/16 gene expression and its biological functions in human cancers to further elucidate the molecular mechanisms of its antitumor effects.
Topics: 3' Untranslated Regions; Animals; Apoptosis; Binding Sites; Biomarkers, Tumor; Cell Movement; Cell Proliferation; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Multigene Family; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Neovascularization, Pathologic; Signal Transduction
PubMed: 30246332
DOI: 10.1002/jcp.27342 -
Role of human DNA2 (hDNA2) as a potential target for cancer and other diseases: A systematic review.DNA Repair Nov 2017DNA nuclease/helicase 2 (DNA2), a multi-functional protein protecting the high fidelity of genomic transmission, plays critical roles in DNA replication and repair... (Review)
Review
DNA nuclease/helicase 2 (DNA2), a multi-functional protein protecting the high fidelity of genomic transmission, plays critical roles in DNA replication and repair processes. In the maturation of Okazaki fragments, DNA2 acts synergistically with other enzymes to cleave the DNA-RNA primer flaps via different pathways. DNA2 is also involved in the stability of mitochondrial DNA and the maintenance of telomeres. Moreover, DNA2 potentially participates in controlling the cell cycle by repairing the DNA replication faults at main checkpoints. In addition, previous evidences demonstrated that DNA2 also functions in the repair process of DNA damages, such as base excision repair (BER). Currently, large studies revealed the structures and functions of DNA2 in prokaryotes and unicellular eukaryotes, such as bacteria and yeast. However, the studies that highlighted the functions of human DNA2 (hDNA2) and the relationships with other multifunctional proteins are still elusive, and more precise investigations are immensely needed. Therefore, this review mainly encompasses the key functions of DNA2 in human cells with various aspects, especially focusing on the genome integrity, and also generalizes the recent insights to the mechanisms related to the occurrence of cancer and other diseases potentially linked to the mutations in DNA2.
Topics: DNA Helicases; DNA Repair; DNA Replication; DNA, Neoplasm; Humans; Mutation; Neoplasms
PubMed: 28903076
DOI: 10.1016/j.dnarep.2017.09.001 -
Aquatic Toxicology (Amsterdam,... Apr 2017The appropriate selection of reference genes for the normalization of non-biological variance in reverse transcription real-time quantitative PCR (RT-qPCR) is essential... (Meta-Analysis)
Meta-Analysis Review
Validation of reference genes for RT-qPCR in marine bivalve ecotoxicology: Systematic review and case study using copper treated primary Ruditapes philippinarum hemocytes.
The appropriate selection of reference genes for the normalization of non-biological variance in reverse transcription real-time quantitative PCR (RT-qPCR) is essential for the accurate interpretation of the collected data. The use of multiple validated reference genes has been shown to substantially increase the robustness of the normalization. It is therefore considered good practice to validate putative genes under specific conditions, determine the optimal number of genes to be employed, and report the method or methods used. Under this premise, we assessed the current state of reference gene based normalization in RT-qPCR bivalve ecotoxicology studies (post 2011), employing a systematic quantitative literature review. A total of 52 papers met our criteria and were analysed for genes used, the use of multiple reference genes, as well as the validation method employed. We further critically discuss methods for reference gene validation based on a case study using copper exposed primary hemocytes from the marine bivalve Ruditapes philippinarum; including the established algorithms geNorm, NormFinder and BestKeeper, as well as the popular online tool RefFinder. We identified that RT-qPCR normalization is largely performed using single reference genes, while less than 40% of the studies attempted to experimentally validate the expression stability of the genes used. 18s rRNA and β-Actin were the most popular genes, yet their un-validated use did introduce artefactual variance that altered the interpretation of the resulting data. Our findings further suggest that combining the results from multiple individual algorithms and calculating the overall best-ranked gene, as computed by the RefFinder tool, does not by default lead to the identification of the most suitable reference genes.
Topics: Animals; Aquatic Organisms; Biomarkers; Bivalvia; Cathepsin D; Copper; Ecotoxicology; Gene Expression Profiling; Gene Expression Regulation; Hemocytes; Humans; RNA; Real-Time Polymerase Chain Reaction; Reference Standards; Reproducibility of Results; Software; Water Pollutants, Chemical
PubMed: 28189915
DOI: 10.1016/j.aquatox.2017.01.003