m6A

Regulating nuclear export precisely is essential for maintaining mRNA homeostasis and impacts tumor progression. However, the mechanisms governing nuclear mRNA export remain poorly elucidated. Herein, it is revealed that the enhanced hypoxic long no-ncoding RNA (lncRNA prostate cancer associated transcript 6 (PCAT6) in breast cancer (BC) promotes the nuclear export of m6A-modified mRNAs, bolstering breast cancer stem cells (BCSCs) stemness and doxorubicin resistance. Clinically, hypoxic PCAT6 correlates with malignant BC features and poor prognosis...

Cancer-associated fibroblasts (CAFs) can promote the crosstalk between cancer cells and tumor microenvironment by exosomes. METTL3-mediated N6-methyladenine (m6A) modification has been proved to promote the progression of non-small cell lung cancer (NSCLC). Here, we focused on the impacts of CAFs-derived exosomes and METTL3-mediated m6A modification on NSCLC progression. Functional analyses were conducted using Cell Counting Kit-8, EdU, colony formation, sphere formation and transwell assays, respectively. Glutamine metabolism was evaluated by detecting glutamate consumption, and the production of intercellular glutamate and α-ketoglutarate (α-KG)...

Recent years have seen rising mortality rates linked to cutaneous melanoma (SKCM), despite advances in immunotherapy. Understanding RNA N6-methyladenosine (M6A) significance in SKCM is crucial for prognosis, tumor microenvironment (TME), immune cell presence, and immunotherapy efficacy. We analyzed 23 M6A regulators using SKCM samples from TCGA and GEO databases, identifying three M6A modification patterns linked to TME cell infiltration. Principal component analysis (PCA) yielded an M6A score for individual tumors, utilizing patient gene expression profiles and CNV data from TCGA...

BACKGROUND: Liver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and is frequently observed during war wounds and trauma. Hepatocyte ferroptosis plays a critical role in liver I/R injury, however, it remains unclear whether this process is controlled or regulated by members of the DEAD/DExH-box helicase (DDX/DHX) family. METHODS: The expression of DDX/DHX family members during liver I/R injury was screened using transcriptome analysis...

N6-methyladenosine (m6A) is the most abundant mRNA modification within mammalian cells, holding pivotal significance in the regulation of mRNA stability, translation and splicing. Furthermore, it plays a critical role in the regulation of RNA degradation by primarily recruiting the YTHDF2 reader protein. However, the selective regulation of mRNA decay of the m6A-methylated mRNA through YTHDF2 binding is poorly understood. To improve our understanding, we developed m6A-BERT-Deg, a BERT model adapted for predicting YTHDF2-mediated degradation of m6A-methylated mRNAs...

N6-methyladenosine (m6A) is a common posttranscriptional RNA modification and plays an important role in cancer biology. Circular RNAs (circRNAs) are also reported to participate in lung adenocarcinoma (LUAD) progression. Here, we aimed to investigate the functions of Wilms tumor 1-associating protein (WTAP) methyltransferase and circEEF2 in LUAD cell tumorigenesis, and probe whether circEEF2 functioned through WTAP-induced m6A modification and its potential mechanisms. Functional analyses were conducted by tube formation, sphere formation, 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, and transwell assays in vitro as well as tumor formation experiments in mice, respectively...

N6-Methyladenosine (m6A), a prevalent posttranscriptional modification, plays an important role in cancer progression. Clear cell renal cell carcinoma (ccRCC) is chiefly associated with the loss of the von Hippel-Lindau (VHL) gene, encoding a component of the E3 ubiquitin ligase complex. In this issue of the JCI, Zhang and colleagues unveiled a function of VHL beyond its canonical role as an E3 ubiquitin ligase in regulating hypoxia-inducible factors (HIFs). It also governed m6A modification by orchestrating the assembly of m6A writer proteins METTL3 and METTL14, thereby stabilizing PIK3R3 mRNA...

N6-Methyladenosine (m6A) is the most abundant posttranscriptional modification, and its contribution to cancer evolution has recently been appreciated. Renal cancer is the most common adult genitourinary cancer, approximately 85% of which is accounted for by the clear cell renal cell carcinoma (ccRCC) subtype characterized by VHL loss. However, it is unclear whether VHL loss in ccRCC affects m6A patterns. In this study, we demonstrate that VHL binds and promotes METTL3/METTL14 complex formation while VHL depletion suppresses m6A modification, which is distinctive from its canonical E3 ligase role...

BACKGROUND: Increasing evidence has demonstrated that N6-methyladenosine (m6 A) RNA modification plays an essential role in a wide range of pathological conditions. Impaired autophagy is a critical hallmark of acute pancreatitis (AP). AIM: To explore the role of the m6 A modification of ZKSCAN3 in the regulation of autophagy in AP. METHODS: The AP mouse cell model was established by cerulein-treated mouse pancreatic acinar cells (MPC-83), and the results were confirmed by the levels of amylase and inflammatory factors...

Development of non-surgical treatment of human abdominal aortic aneurysm (AAA) has clinical significance. Colchicine emerges as an effective therapeutic regimen in cardiovascular diseases. Yet, whether colchicine slows AAA growth remain controversy. Here, we demonstrated that daily intragastric administration of low-dose colchicine blocked AAA formation, prevented vascular smooth muscle cell (SMC) phenotype switching and apoptosis, and vascular inflammation in both peri-aortic CaPO4 injury and subcutaneous angiotensin-II infusion induced experimental AAA mice models...

BACKGROUND: Breast cancer (BC/BRCA) is the most common carcinoma in women. The average 5-year survival rate of BC patients with stage IV disease is 26%. A considerable proportion of patients still do not receive effective therapy. It is an unmet need to identify novel biomarkers for BC patients. Herein, we evaluated whether the programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) status is associated with the clinical outcomes of BC, based on data from The Cancer Genome Atlas (TCGA)...

Colorectal cancer (CRC) ranks as the third most prevalent malignancy worldwide. Despite the gradual expansion of therapeutic options for CRC, its clinical management remains a formidable challenge. And, because of the current dearth of technical means for early CRC screening, most patients are diagnosed at an advanced stage. Therefore, it is imperative to develop novel diagnostic and therapeutic tools for this disease. N6-methyladenosine (m6A), the predominant RNA modification in eukaryotes, can be recognized by m6A-specific methylated reading proteins to modulate gene expression...

Fibrosis is a pathological phenomenon characterized by the aberrant accumulation of extracellular matrix (ECM) in tissues. Fibrosis is a universally age-related disease involving that many organs and is the final stage of many chronic inflammatory diseases, which often threaten the patient's health. Undoubtedly, fibrosis has become a serious economic and health burden worldwide, However, the pathogenesis of fibrosis is complex. Further, the key molecules still remain to be unraveled. Hence, so far, there have been no effective treatments designed against the key targets of fibrosis...

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, it has a poor prognosis due to its highly invasive and metastatic nature. Consequently, identifying effective prognostic markers and potential therapeutic targets has been extensively investigated. METTL5, an 18S rRNA methyltransferase, is abnormally high in HCC. But its biological function and prognostic significance in HCC remain largely unelucidated. This study aimed to investigate the role of METTL5 in HCC progression, and elucidate its possible molecular mechanisms in HCC via transcriptome sequencing, providing new insights for identifying new HCC prognostic markers and therapeutic targets...

N 6 -methyladenosine (m6 A) is a prevalent internal modification in eukaryotic mRNA, tRNA, miRNA, and long non-coding RNA. It is also known for its role in plant responses to biotic and abiotic stresses. However, a comprehensive m6 A transcriptome-wide map for Puccinia striiformis f. sp. tritici ( Pst ) infections in wheat ( Triticum aestivum ) is currently unavailable. Our study is the first to profile m6 A modifications in wheat infected with a virulent Pst race. Analysis of RNA-seq and MeRIP-seq data revealed that the majority of differentially expressed genes are up-regulated and hyper-methylated...

N6-methyladenosine (m6A) methylation, a prevalent epitranscriptomic modification, plays a crucial role in regulating mRNA expression, stability, and translation in mammals. M6A regulators have gained attention for their potential implications in tumorigenesis and clinical applications, such as cancer diagnosis and therapeutics. The existing literature predominantly addresses m6A regulators in the context of primary prostate cancer (PCa). However, a notable gap in the knowledge emerges regarding the dynamic expression patterns of these regulators as PCa progresses towards the castration-resistant stage (CRPC)...

Benzene is a known contributor to human leukaemia through its toxic effects on bone marrow cells, and epigenetic modification is believed to be a potential mechanism underlying benzene pathogenesis. However, the specific roles of N6-methyladenosine (m6A), a newly discovered RNA post-transcriptional modification, in benzene-induced hematotoxicity remain unclear. In this study, we identified self-renewing malignant proliferating cells in the bone marrow of benzene-exposed mice through in vivo bone marrow transplantation experiments and Competitive Repopulation Assay...

METTL3, a primary methyltransferase catalyzing RNA N6-methyladenosine (m6A) modification, has been identified as an oncogene in several cancer types and thus nominated as a potentially effective target for therapeutic inhibition, although current options using this strategy are limited. In this study, we targeted protein-protein interactions at the METTL3-METTL14 binding interface to inhibit complex formation and subsequent catalysis of RNA m6A modification. Among candidate peptides, RM3 exhibited the highest anti-cancer potency, inhibiting METTL3 activity while also facilitating its proteasomal degradation...

PURPOSE: This study aimed to investigate the effect of the N6-methyladenosine (m6A) dependent ferroptosis on cisplatininduced Sertoli cell injury. MATERIALS AND METHODS: A cisplatin exposure mouse model was established by intraperitoneal injection of cisplatin in our study. TM4 cell lines was used for in vitro study. Ferroptosis was detected according to metabolomic analysis and a series of assays, including malondialdehyde, glutathione, and glutathione disulfide concentration detection, 2',7'-dichlorodihydrofluorescein diacetate and BODIPY 581/591 C11 probe detection, and transmission electron microscope imaging...

Myocardial ischemia‒reperfusion injury (MI/RI) is closely related to pyroptosis. alkB homolog 5 (ALKBH5) is abnormally expressed in the MI/RI models. However, the detailed molecular mechanism of ALKBH5 in MI/RI has not been elucidated. In this study, rats and H9C2 cells served as experimental subjects and received MI/R induction and H/R induction, respectively. The abundance of the targeted molecules was evaluated using RT-qPCR, Western blotting, immunohistochemistry, immunofluorescence, and enzyme-linked immunosorbent assay...