scholarly journals Current Advances in N6-Methyladenosine Methylation Modification During Bladder Cancer

2022 ◽  
Vol 12 ◽  
Author(s):  
Qiang Liu
Keyword(s):  
Bladder Cancer ◽  
Messenger Rna ◽  
Incidence Rates ◽  
Tumor Formation ◽  
Rna Methylation ◽  
Pathological Type ◽  
Bladder Urothelial Carcinoma ◽  
High Incidence ◽  
M6a Rna Methylation ◽  
Well Differentiated

N6-methyladenosine (m6A) is a dynamic, reversible post-transcriptional modification, and the most common internal modification of eukaryotic messenger RNA (mRNA). Considerable evidence now shows that m6A alters gene expression, thereby regulating cell self-renewal, differentiation, invasion, and apoptotic processes. M6A methylation disorders are directly related to abnormal RNA metabolism, which may lead to tumor formation. M6A methyltransferase is the dominant catalyst during m6A modification; it removes m6A demethylase, promotes recognition by m6A binding proteins, and regulates mRNA metabolic processes. Bladder cancer (BC) is a urinary system malignant tumor, with complex etiology and high incidence rates. A well-differentiated or moderately differentiated pathological type at initial diagnosis accounts for most patients with BC. For differentiated superficial bladder urothelial carcinoma, the prognosis is normally good after surgery. However, due to poor epithelial cell differentiation, BC urothelial cell proliferation and infiltration may lead to invasive or metastatic BC, which lowers the 5-years survival rate and significantly affects clinical treatments in elderly patients. Here, we review the latest progress in m6A RNA methylation research and investigate its regulation on BC occurrence and development.

scholarly journals The Role of m6A Ribonucleic Acid Modification in the Occurrence of Atherosclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Jie Fu ◽  
Xinghui Cui ◽  
Xiaoyun Zhang ◽  
Min Cheng ◽  
Xiaoxia Li ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Biological Activities ◽  
Rna Modification ◽  
Acid Modification ◽  
Rna Methylation ◽  
Mrna Metabolism ◽  
Modification Process ◽  
M6a Rna Methylation ◽  
The Relationship

The N6-methyladenosine (m6A) modification is the most abundant epitranscriptomic modification in eukaryotic messenger RNA (mRNA). The m6A modification process is jointly regulated by various enzymes and proteins, such as methyltransferases, demethylases and related m6A-binding proteins. The process is dynamic and reversible, and it plays an essential role in mRNA metabolism and various biological activities. Recently, an increasing number of researchers have confirmed that the onset and development of many diseases are closely associated with the molecular biological mechanism of m6A RNA methylation. This study focuses on the relationship between m6A RNA modification and atherosclerosis (AS). It thoroughly summarizes the mechanisms and processes of m6A RNA modification in AS-related cells and the relationships between m6A RNA modification and AS risk factors, and it provides a reference for exploring new targets for the early diagnosis and treatment of AS.

scholarly journals m6A RNA methylation regulators can contribute to malignant progression and impact the prognosis of bladder cancer

2019 ◽  
Vol 39 (12) ◽  
Author(s):  
Mei Chen ◽  
Zhen-yu Nie ◽  
Xiao-hong Wen ◽  
Yuan-hui Gao ◽  
Hui Cao ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Cox Regression ◽  
Risk Group ◽  
High Risk Group ◽  
Malignant Progression ◽  
Low Risk ◽  
Rna Methylation ◽  
M6a Rna Methylation ◽  
Clinicopathological Variables

Abstract N6-methyladenosine (m6A) is the most common form of messenger RNA (mRNA) modification. An increasing number of studies have proven that m6A RNA methylation regulators are overexpressed in many cancers and participate in the development of cancer through the dynamic regulation of m6A RNA methylation regulators. However, the prognostic role of m6A RNA methylation regulators in bladder cancer (BC) is poorly understood. In the present study, we downloaded the mRNA expression data from The Cancer Genome Atlas (TCGA) database and the corresponding clinical and prognostic information. The relationship between m6A RNA methylation regulators and clinicopathological variables of BC patients was assessed by the Kolmogorov–Smirnov test. The expression of the m6A RNA methylation regulators was differentially associated with different clinicopathological variables of BC patients. The least absolute shrinkage and selection operator (LASSO) Cox regression model was then applied to identify three m6A RNA methylation regulators. The risk signature was constructed as follows: 0.164FTO − (0.081YTHDC1+0.032WTAP). Based on the risk signature, the risk score of each patient was calculated, and the patients were divided into a high-risk group and a low-risk group. The overall survival (OS) rate of the high-risk group was significantly lower than that of the low-risk group. The risk signature was not only an independent prognostic marker for BC patients but also a predictor of clinicopathological variables. In conclusion, m6A RNA methylation regulators can participate in the malignant progression of BC, and a risk signature with three selected m6A RNA methylation regulators may be a promising prognostic biomarker to guide personalized treatment for BC patients.

scholarly journals METTL3 counteracts premature aging via m6A-dependent stabilization of MIS12 mRNA

2020 ◽  
Vol 48 (19) ◽  
pp. 11083-11096
Author(s):  
Zeming Wu ◽  
Yue Shi ◽  
Mingming Lu ◽  
Moshi Song ◽  
Zihui Yu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cellular Senescence ◽  
Messenger Rna ◽  
Transcriptional Profiling ◽  
Human Mesenchymal Stem Cell ◽  
Premature Aging ◽  
Biological Processes ◽  
Rna Methylation ◽  
Progeroid Syndromes ◽  
M6a Rna Methylation

Abstract N6-Methyladenosine (m6A) messenger RNA methylation is a well-known epitranscriptional regulatory mechanism affecting central biological processes, but its function in human cellular senescence remains uninvestigated. Here, we found that levels of both m6A RNA methylation and the methyltransferase METTL3 were reduced in prematurely senescent human mesenchymal stem cell (hMSC) models of progeroid syndromes. Transcriptional profiling of m6A modifications further identified MIS12, for which m6A modifications were reduced in both prematurely senescent hMSCs and METTL3-deficient hMSCs. Knockout of METTL3 accelerated hMSC senescence whereas overexpression of METTL3 rescued the senescent phenotypes. Mechanistically, loss of m6A modifications accelerated the turnover and decreased the expression of MIS12 mRNA while knockout of MIS12 accelerated cellular senescence. Furthermore, m6A reader IGF2BP2 was identified as a key player in recognizing and stabilizing m6A-modified MIS12 mRNA. Taken together, we discovered that METTL3 alleviates hMSC senescence through m6A modification-dependent stabilization of the MIS12 transcript, representing a novel epitranscriptional mechanism in premature stem cell senescence.

scholarly journals A new m6A methylation-related gene signature for prognostic value in patient with urothelial carcinoma of the bladder

2021 ◽  
Author(s):  
Bin Zheng ◽  
Jianwei Wang ◽  
Guiting Zhao ◽  
Xiaoxu Chen ◽  
Zhongshun Yao ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Prognostic Value ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Prognostic Indicators ◽  
Rna Methylation ◽  
Human Protein Atlas ◽  
Carcinoma Of The Bladder ◽  
M6a Rna Methylation ◽  
Muscle Invasive

Background: Bladder cancer (BC) is one of the most common malignant urological cancer in the world. Because of its characteristic of easy-recurrence and muscle-invasive, advances in our genetic understanding of bladder cancer should be translated into prognostic indicators. Methods: We investigated 16 m6A RNA methylation regulators from The Cancer Genome Atlas (TCGA) database and The Human Protein Atlas (HPA) database. The expression profile, clinical application as well as prognostic value of these genes in UC were investigated. Moreover, we further explored the correlation between RNA methylation genes and biological functions, pathways and immune status. Results: Five m6A-related genes (HNRNPC, YTHDF2, YTHDF1, HNRNPA2B1, METTL3) upregulated in UC tissues, while three regulators (ZC3H13, METTL16, FTO) downregulated in UC. FTO and YTHDF2 show biomarker potential for the prognosis of UC patients. In addition, these identified genes may related with essential functions and core molecular pathways. Conclusions: Our research shows that two m6A RNA methylation regulators can serve as reliable prognostic biomarkers of UC, which might be exerted as potential targets of therapeutic strategies.

scholarly journals The m6A RNA methylation regulates oncogenic signaling pathways driving cell malignant transformation and carcinogenesis

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Mohammad Burhan Uddin ◽  
Zhishan Wang ◽  
Chengfeng Yang
Keyword(s):  
Signaling Pathways ◽  
Malignant Transformation ◽  
Noncoding Rna ◽  
Rna Modification ◽  
Oncogenic Signaling ◽  
Aberrant Expression ◽  
Rna Methylation ◽  
Rna Molecules ◽  
M6a Rna Methylation ◽  
Oncogenic Signaling Pathways

AbstractThe m6A RNA methylation is the most prevalent internal modification in mammalian mRNAs which plays critical biological roles by regulating vital cellular processes. Dysregulations of the m6A modification due to aberrant expression of its regulatory proteins are frequently observed in many pathological conditions, particularly in cancer. Normal cells undergo malignant transformation via activation or modulation of different oncogenic signaling pathways through complex mechanisms. Accumulating evidence showing regulation of oncogenic signaling pathways at the epitranscriptomic level has added an extra layer of the complexity. In particular, recent studies demonstrated that, in many types of cancers various oncogenic signaling pathways are modulated by the m6A modification in the target mRNAs as well as noncoding RNA transcripts. m6A modifications in these RNA molecules control their fate and metabolism by regulating their stability, translation or subcellular localizations. In this review we discussed recent exciting studies on oncogenic signaling pathways that are modulated by the m6A RNA modification and/or their regulators in cancer and provided perspectives for further studies. The regulation of oncogenic signaling pathways by the m6A modification and its regulators also render them as potential druggable targets for the treatment of cancer.

scholarly journals Temporal and geographic analysis of trichinellosis incidence in Chile with risk assessment

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Carlos Landaeta-Aqueveque ◽  
Salvador Ayala ◽  
Denis Poblete-Toledo ◽  
Mauricio Canals
Keyword(s):  
Relative Risk ◽  
Poverty Rate ◽  
Incidence Rates ◽  
Temporal Data ◽  
Rate Fluctuation ◽  
High Incidence ◽  
Domestic Cycle ◽  
Model Residuals ◽  
Free Ranging ◽  
Spearman’S Correlation

AbstractTrichinellosis is a foodborne disease caused by several Trichinella species around the world. In Chile, the domestic cycle was fairly well-studied in previous decades, but has been neglected in recent years. The aims of this study were to analyze, geographically, the incidence of trichinellosis in Chile to assess the relative risk and to analyze the incidence rate fluctuation in the last decades. Using temporal data spanning 1964–2019, as well as geographical data from 2010 to 2019, the time series of cases was analyzed with ARIMA models to explore trends and periodicity. The Dickey-Fuller test was used to study trends, and the Portmanteau test was used to study white noise in the model residuals. The Besag-York-Mollie (BYM) model was used to create Bayesian maps of the level of risk relative to that expected by the overall population. The association of the relative risk with the number of farmed swine was assessed with Spearman’s correlation. The number of annual cases varied between 5 and 220 (mean: 65.13); the annual rate of reported cases varied between 0.03 and 1.9 cases per 105 inhabitants (mean: 0.53). The cases of trichinellosis in Chile showed a downward trend that has become more evident since the 1980s. No periodicities were detected via the autocorrelation function. Communes (the smallest geographical administrative subdivision) with high incidence rates and high relative risk were mostly observed in the Araucanía region. The relative risk of the commune was significantly associated with the number of farmed pigs and boar (Sus scrofa Linnaeus, 1758). The results allowed us to state that trichinellosis is not a (re)emerging disease in Chile, but the severe economic poverty rate of the Mapuche Indigenous peoples and the high number of backyard and free-ranging pigs seem to be associated with the high risk of trichinellosis in the Araucanía region.

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