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 Long Noncoding RNA H19: A Novel Therapeutic Target Emerging in Oncology Via Regulating Oncogenic Signaling Pathways

2021 ◽  
Vol 9 ◽  
Author(s):  
Baokang Wu ◽  
Yizhou Zhang ◽  
Yang Yu ◽  
Chongli Zhong ◽  
Qi Lang ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Therapeutic Target ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Regulatory Function ◽  
Migration And Invasion ◽  
Oncogenic Signaling ◽  
Regulatory Relationship ◽  
Oncogenic Signaling Pathways ◽  
Novel Therapeutic

Long noncoding RNA H19 (H19) is an imprinting gene with only maternal expression that is involved in regulating different processes in various types of cells. Previous studies have shown that abnormal H19 expression is involved in many pathological processes, such as cancer, mainly through sponging miRNAs, interacting with proteins, or regulating epigenetic modifications. Accumulating evidence has shown that several oncogenic signaling pathways lead to carcinogenesis. Recently, the regulatory relationship between H19 and oncogenic signaling pathways in various types of cancer has been of great interest to many researchers. In this review, we discussed the key roles of H19 in cancer development and progression via its regulatory function in several oncogenic signaling pathways, such as PI3K/Akt, canonical Wnt/β-catenin, canonical NF-κB, MAPK, JAK/STAT and apoptosis. These oncogenic signaling pathways regulated by H19 are involved in cell proliferation, proliferation, migration and invasion, angiogenesis, and apoptosis of various cancer cells. This review suggests that H19 may be a novel therapeutic target for cancers treatment by regulating oncogenic signaling pathways.

scholarly journals The Prognostic Values of m6A RNA Methylation Regulators in Thyroid Carcinoma

2020 ◽  
Author(s):  
Di Zhang ◽  
Yue Ma ◽  
Xu-Chen Cao ◽  
Li Fu ◽  
Yue Yu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Ontology ◽  
Thyroid Carcinoma ◽  
Signaling Pathways ◽  
Rna Modification ◽  
Consensus Clustering ◽  
Gene Set Enrichment ◽  
Rna Methylation ◽  
Gene Set ◽  
M6a Rna Methylation

Abstract Background: N6-methyladenosine (m6A) is the most common RNA modification and regulates RNA splicing, translation, translocation, and stability. Aberrant expression of m6A has been reported in various types of human cancers. m6A RNA modification is dynamically and reversibly mediated by different regulators, including methyltransferase, demethylases, and m6A binding proteins. However, the role of m6A RNA methylation regulators in thyroid cancer remains unknown. The aim of this study is to investigate the effect of the 13 main m6A RNA modification regulators in thyroid carcinoma.Methods: The gene expression profile of m6A RNA modification regulations and clinical information of patients with thyroid carcinoma were obtained from The Cancer Genome Atlas database. Consensus clustering was applied to identify two clusters of thyroid carcinomas with different clinical outcome. LASSO Cox regression analysis was used to construct gene-based prognostic signature based on the expression of m6A RNA methylation regulators. Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and gene set enrichment analyses were performed to explore differential cellular processes and signaling pathways between the two groups based on risk signature.Results: We found that most of the m6A RNA modification regulators are down-regulated in 450 patients with thyroid carcinoma. We identified two clusters based on the gene expression profiles of 13 m6A RNA modification regulators using consensus clustering. The cluster 2 subgroup correlates with an unfavorable outcome compared with the cluster 1 subgroup. In addition, we derived a three m6A RNA modification regulator genes-based risk signature (FTO, RBM15 and KIAA1429), that is an independent prognostic biomarker in patients with thyroid carcinoma. There were significantly different signaling pathways between high and low risk group by Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and gene set enrichment analyses. Moreover, we found that this risk signature could better predict outcome in male than female. Conclusion: Our study revealed the prognostic value of m6A RNA methylation regulators in patients with thyroid carcinoma.

scholarly journals The functions and prognostic values of m6A RNA methylation regulators in thyroid carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhi-Hao Yu ◽  
Shao-Ting Feng ◽  
Di Zhang ◽  
Xu-Chen Cao ◽  
Yue Yu ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
Rna Modification ◽  
Sequencing Data ◽  
Aberrant Expression ◽  
Cox Regression Analysis ◽  
Rna Methylation ◽  
M6a Rna Methylation

Abstract Background N6-Methyladenosine (m6A) is the most common RNA modification and regulates RNA splicing, translation, translocation, and stability. Aberrant expression of m6A has been reported in various types of human cancers. m6A RNA modification is dynamically and reversibly mediated by different regulators, including methyltransferase, demethylases, and m6A binding proteins. However, the role of m6A RNA methylation regulators in thyroid cancer remains unknown. The aim of this study is to investigate the effect of the 13 main m6A RNA modification regulators in thyroid carcinoma. Methods We obtained clinical data and RNA sequencing data of 13 m6A RNA methylation regulators from The Cancer Genome Atlas (TCGA) THCA database. We performed consensus clustering to identify the clinical relevance of m6A RNA methylation regulators in thyroid carcinoma. Then we used LASSO Cox regression analysis to generate a prognostic signature based on m6A RNA modification regulator expression. Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and Gene Set Enrichment Analyses were performed to explore differential cellular processes and signaling pathways between the two groups based on risk signature. Results We found that most of the m6A RNA modification regulators are down-regulated in 450 patients with thyroid carcinoma. We derived a three m6A RNA modification regulator genes-based risk signature (FTO, RBM15 and KIAA1429), that is an independent prognostic biomarker in patients with thyroid carcinoma. Moreover, we found that this risk signature could better predict outcome in male than female. Functional research in vitro demonstrated that the m6A RNA methylation regulators involved in the model acted significant role in the proliferation and migration of thyroid cancer cells. Conclusions Our study revealed the influence of m6A RNA methylation regulators on thyroid carcinoma through biological experiments and three-gene prognostic model.

MALAT1 as a Versatile Regulator of Cancer: Overview of the updates from Predatory role as Competitive Endogenous RNA to Mechanistic In-sights

2020 ◽  
Vol 20 ◽  
Author(s):  
Ammad Ahmad Farooqi ◽  
Evangelia Legaki ◽  
Maria Gazouli ◽  
Silvia Rinaldi ◽  
Rossana Berardi
Keyword(s):  
Molecular Biology ◽  
Detailed Analysis ◽  
Signaling Pathways ◽  
Individualized Medicine ◽  
Signaling Cascades ◽  
Oncogenic Signaling ◽  
Non Coding Rnas ◽  
Oncogenic Signaling Pathways ◽  
Competitive Endogenous Rna

: Central dogma of molecular biology has remained cornerstone of classical molecular biology but serendipitous discovery of microRNAs (miRNAs) in nematodes paradigmatically shifted our current understanding of the intricate mech-anisms which occur during transitions from transcription to translation. Discovery of miRNA captured tremendous attention and appreciation and we had witnessed an explosion in the field of non-coding RNAs. Ground-breaking discoveries in the field of non-coding RNAs have helped in better characterization of microRNAs and long non-coding RNAs (LncRNAs). There is an ever-increasing list of miRNA targets which are regulated by MALAT1 to stimulate or repress expression of tar-get genes. However, in this review our main focus is to summarize mechanistic insights related to MALAT1-mediated regu-lation of oncogenic signaling pathways. We have discussed how MALAT1 modulated TGF/SMAD and Hippo pathways in various cancers. We have also comprehensively summarized how JAK/STAT and Wnt/β-catenin pathways stimulated MALAT1 expression and consequentially how MALAT1 potentiated these signaling cascades to promote cancer. MALAT1 research has undergone substantial broadening however, there is still a need to identify additional mechanisms. MALAT1 is involved in multi-layered regulation of multiple transduction cascades and detailed analysis of different pathways will be helpful in getting a step closer to individualized medicine.

scholarly journals N6-Methyladenosine RNA modification in cerebrospinal fluid as a novel potential diagnostic biomarker for progressive multiple sclerosis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Fei Ye ◽  
Tianzhu Wang ◽  
Xiaoxin Wu ◽  
Jie Liang ◽  
Jiaoxing Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Clustering Analysis ◽  
Roc Curves ◽  
Progressive Multiple Sclerosis ◽  
Rna Modification ◽  
Diagnostic Model ◽  
Consensus Clustering ◽  
Rna Methylation ◽  
M6a Rna Methylation

Abstract Background Progressive multiple sclerosis (PMS) is an uncommon and severe subtype of MS that worsens gradually and leads to irreversible disabilities in young adults. Currently, there are no applicable or reliable biomarkers to distinguish PMS from relapsing–remitting multiple sclerosis (RRMS). Previous studies have demonstrated that dysfunction of N6-methyladenosine (m6A) RNA modification is relevant to many neurological disorders. Thus, the aim of this study was to explore the diagnostic biomarkers for PMS based on m6A regulatory genes in the cerebrospinal fluid (CSF). Methods Gene expression matrices were downloaded from the ArrayExpress database. Then, we identified differentially expressed m6A regulatory genes between MS and non-MS patients. MS clusters were identified by consensus clustering analysis. Next, we analyzed the correlation between clusters and clinical characteristics. The random forest (RF) algorithm was applied to select key m6A-related genes. The support vector machine (SVM) was then used to construct a diagnostic gene signature. Receiver operating characteristic (ROC) curves were plotted to evaluate the accuracy of the diagnostic model. In addition, CSF samples from MS and non-MS patients were collected and used for external validation, as evaluated by an m6A RNA Methylation Quantification Kit and by real-time quantitative polymerase chain reaction. Results The 13 central m6A RNA methylation regulators were all upregulated in MS patients when compared with non-MS patients. Consensus clustering analysis identified two clusters, both of which were significantly associated with MS subtypes. Next, we divided 61 MS patients into a training set (n = 41) and a test set (n = 20). The RF algorithm identified eight feature genes, and the SVM method was successfully applied to construct a diagnostic model. ROC curves revealed good performance. Finally, the analysis of 11 CSF samples demonstrated that RRMS samples exhibited significantly higher levels of m6A RNA methylation and higher gene expression levels of m6A-related genes than PMS samples. Conclusions The dynamic modification of m6A RNA methylation is involved in the progression of MS and could potentially represent a novel CSF biomarker for diagnosing MS and distinguishing PMS from RRMS in the early stages of the disease.

Deguelin targets multiple oncogenic signaling pathways to combat human malignancies

2021 ◽  
Vol 166 ◽  
pp. 105487
Author(s):  
Hardeep Singh Tuli ◽  
Sonam Mittal ◽  
Mariam Loka ◽  
Vaishali Aggarwal ◽  
Diwakar Aggarwal ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Oncogenic Signaling ◽  
Oncogenic Signaling Pathways

scholarly journals Current insights into the implications of m6A RNA methylation and autophagy interaction in human diseases

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xuechai Chen ◽  
Jianan Wang ◽  
Muhammad Tahir ◽  
Fangfang Zhang ◽  
Yuanyuan Ran ◽  
...  
Keyword(s):  
Intervertebral Disc Degeneration ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Degradation Process ◽  
Human Diseases ◽  
Rna Modification ◽  
Rna Methylation ◽  
M6a Rna Methylation ◽  
The Impact

AbstractAutophagy is a conserved degradation process crucial to maintaining the primary function of cellular and organismal metabolism. Impaired autophagy could develop numerous diseases, including cancer, cardiomyopathy, neurodegenerative disorders, and aging. N6-methyladenosine (m6A) is the most common RNA modification in eukaryotic cells, and the fate of m6A modified transcripts is controlled by m6A RNA binding proteins. m6A modification influences mRNA alternative splicing, stability, translation, and subcellular localization. Intriguingly, recent studies show that m6A RNA methylation could alter the expression of essential autophagy-related (ATG) genes and influence the autophagy function. Thus, both m6A modification and autophagy could play a crucial role in the onset and progression of various human diseases. In this review, we summarize the latest studies describing the impact of m6A modification in autophagy regulation and discuss the role of m6A modification-autophagy axis in different human diseases, including obesity, heart disease, azoospermatism or oligospermatism, intervertebral disc degeneration, and cancer. The comprehensive understanding of the m6A modification and autophagy interplay may help in interpreting their impact on human diseases and may aid in devising future therapeutic strategies.

scholarly journals The role of m6A modification in the biological functions and diseases

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Xiulin Jiang ◽  
Baiyang Liu ◽  
Zhi Nie ◽  
Lincan Duan ◽  
Qiuxia Xiong ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Rna Modification ◽  
Biological Functions ◽  
Rna Methylation ◽  
Downstream Target ◽  
Different Types ◽  
M6a Rna Methylation

AbstractN6-methyladenosine (m6A) is the most prevalent, abundant and conserved internal cotranscriptional modification in eukaryotic RNAs, especially within higher eukaryotic cells. m6A modification is modified by the m6A methyltransferases, or writers, such as METTL3/14/16, RBM15/15B, ZC3H3, VIRMA, CBLL1, WTAP, and KIAA1429, and, removed by the demethylases, or erasers, including FTO and ALKBH5. It is recognized by m6A-binding proteins YTHDF1/2/3, YTHDC1/2 IGF2BP1/2/3 and HNRNPA2B1, also known as “readers”. Recent studies have shown that m6A RNA modification plays essential role in both physiological and pathological conditions, especially in the initiation and progression of different types of human cancers. In this review, we discuss how m6A RNA methylation influences both the physiological and pathological progressions of hematopoietic, central nervous and reproductive systems. We will mainly focus on recent progress in identifying the biological functions and the underlying molecular mechanisms of m6A RNA methylation, its regulators and downstream target genes, during cancer progression in above systems. We propose that m6A RNA methylation process offer potential targets for cancer therapy in the future.

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.

Diagnostic, prognostic, and therapeutic value of miR-148b in human cancers

2021 ◽  
Vol 21 ◽  
Author(s):  
Afsane Bahrami ◽  
Gordon A. Ferns
Keyword(s):  
Gene Expression ◽  
Tumor Suppressor ◽  
Noncoding Rna ◽  
Clinical Importance ◽  
Aberrant Expression ◽  
Rna Molecules ◽  
Small Noncoding Rna ◽  
Human Cancers ◽  
Therapeutic Value ◽  
Cancer Types

: MicroRNAs (miRs) is a class of conserved, small, noncoding RNA molecules which modulate gene expression post-transcriptionally. miR-148b is a member of miR-148/152 family generally known to be a tumor suppressor via its affect on different signaling pathways and regulatory genes. Aberrant expression of miR-148b has recently been shown to be responsible for tumorigenesis for several different cancer types. This review discusses the current evidences regarding the involvement of miR-148b expression in human cancers and its potential clinical importance for tumor diagnosis, prognosis, and therapeutics.

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