N6-methyladenosine (m6A) methyltransferase METTL3 regulates sepsis-induced myocardial injury through IGF2BP1/HDAC4 dependent manner

Cell Death Discovery, Journal Year: 2022, Volume and Issue: 8(1)

Published: July 15, 2022

Abstract Recent studies have identified that N 6 -methyladenosine (m A) extensively participates in the myocardial injury pathophysiological process. However, role of m A on sepsis-induced is still unclear. Here, we investigated functions and mechanism methyltransferase METTL3 for septic injury. Results illustrated modification level up-regulated lipopolysaccharide (LPS)-induced cardiomyocytes (H9C2 cells). Methylated RNA immunoprecipitation sequencing (MeRIP-Seq) revealed profile cellular model. Functionally, knockdown repressed inflammatory damage induced by LPS. Mechanistically, found HDAC4 had remarkable sites its 3’-UTR genome, acting as downstream target METTL3. Besides, reader IGF2BP1 recognized mRNA enhanced stability. In conclusion, findings a METTL3/IGF2BP1/m A/HDAC4 axis injury, which might provide novel therapeutic strategy

Language: Английский

---

NcRNAs: Multi‑angle participation in the regulation of glioma chemotherapy resistance (Review)

International Journal of Oncology, Journal Year: 2022, Volume and Issue: 60(6)

Published: May 4, 2022

As the most common primary tumour of central nervous system, gliomas have a high recurrence rate after surgical resection and are resistant to chemotherapy, particularly high‑grade dominated by glioblastoma multiforme (GBM). The prognosis GBM remains poor despite improvements in treatment modalities, posing serious threat human health. At present, although drugs such as temozolomide, cisplatin bevacizumab, effective improving overall survival patients with GBM, eventually develop drug resistance, leading clinical prognosis. development multidrug resistance has therefore become major obstacle effectiveness chemotherapy for GBM. ability fully understand underlying mechanisms novel therapeutic targets overcome is critical Of note, growing evidence indicates that large number abnormally expressed noncoding RNAs (ncRNAs) role glioma chemoresistance may target various modulate chemosensitivity. In present review, roles molecular ncRNAs were systematically summarized, potential markers discussed prospects outlined. research direction tumor targeted therapies, which not only provides perspectives reversing but also promote precision medicine diagnosis treatment.

Language: Английский

---

METTL14 is Involved in TNF-α-Induced Inflammation in Colorectal Epithelial Cells via Autophagy Modulation

Applied Biochemistry and Biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: June 15, 2024

Language: Английский

---

Identification of RNA Methylation-Related lncRNAs Signature for Predicting Hot and Cold Tumors and Prognosis in Colon Cancer

Frontiers in Genetics, Journal Year: 2022, Volume and Issue: 13

Published: April 6, 2022

N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), and 7-methylguanosine (m7G) are the major forms of RNA methylation modifications, which closely associated with development many tumors. However, prognostic value methylation-related long non-coding RNAs (lncRNAs) in colon cancer (CC) has not been defined. This study summarised 50 m6A/m1A/m5C/m7G-related genes downloaded 41 normal 471 CC tumor samples RNA-seq data clinicopathological information from The Cancer Genome Atlas (TCGA) database. A total 1057 lncRNAs (RMlncRNAs) were identified Pearson correlation analysis. Twenty-three RMlncRNAs values screened using univariate Cox regression By consensus clustering analysis, patients classified into two molecular subtypes (Cluster 1 Cluster 2) different clinical outcomes immune microenvironmental infiltration characteristics. 2 was considered to be "hot tumor" a better prognosis, while cluster regarded as "cold poorer prognosis. Subsequently, we constructed seven-lncRNA signature least absolute shrinkage selection operator (LASSO) regression. In combination other traits, found that lncRNA (called "RMlnc-score") an independent factor for cancer. addition, infiltration, immunotherapy response half-maximum inhibitory concentration (IC50) showed low RMlnc-score group more sensitive immunotherapy, high chemotherapeutic agents. summary, developed could used predict response, drug sensitivity patients, guiding accurate, personalized treatment regimens.

Language: Английский

---

Uncovering the Regulatory Role of Long Non-Coding RNAs in Colorectal Cancer Progression and Liver Metastasis: Implications for Therapeutic and Diagnostic Targeting

Afghanistan Journal of Basic Medical Science, Journal Year: 2025, Volume and Issue: 2(1), P. 1 - 15

Published: Jan. 17, 2025

Background: Colorectal cancer (CRC) is a leading cause of cancer-related deaths, largely due to metastasis, particularly the liver, and limited understanding molecular mechanisms underlying this process. In study, we aimed investigate role long non-coding Methods: RNAs (lncRNAs) are key regulatory factors in CRC progression metastasis liver tissues. Using high-throughput sequencing microarray approaches, analyzed gene expression profiles from two independent lncRNA datasets identify potential players involved metastasis. Results: Our findings revealed five lncRNAs—PROX1-AS1, SOX9-AS1, LINC01594, LINC01555, APOA1-AS—previously known for their roles progression, now identified as being metastatic Additionally, 20 other lncRNAs, including VCAN-AS1, SYP-AS1, SMIM2-IT1, NCOA7-AS1, LINC01449, were also contributors Notably, lncRNAs—SATB2-AS1 LINC01116—emerged common candidates across both datasets, suggesting significant promoting liver. These lncRNAs hold promise targets therapeutic diagnostic development. Conclusion: study uncovers novel layer involving advance our behaviors that drive offer new avenues targeted strategies tools, CRC.

Language: Английский

---

Novel insight into the functions of N⁶‑methyladenosine modified lncRNAs in cancers (Review)

International Journal of Oncology, Journal Year: 2022, Volume and Issue: 61(6)

Published: Oct. 19, 2022

Emerging evidence has suggested that N⁶‑methyladenosine (m6A) modification, a typical RNA methylation controls the fate of modified transcripts and is involved in pathogenesis various human diseases, such as metabolic disorders, nephropathology, osteoarthritis malignant tumours. Long noncoding RNAs (lncRNAs), >200 nt length, have also been indicated to be diseases by participating processes epigenetic modifications, transcriptional alternations posttranslational regulation. Recent studies revealed lncRNAs were widely m6A, which critical role cellular are associated with numerous particularly cancers. The present review first examined functions m6A modification lncRNAs, including changing lncRNA structure, mediating regulation, affecting mRNA precursor splicing, regulating stability translation. Furthermore, regulatory mechanisms m6A‑modified cancers summarized up‑to‑date detection methods prediction tools for identifying sites on presented. In addition, viewpoints potential future directions field discussed, more accurate methods, roles lncRNAs‑encoded micropeptides cancers, relationship between tumour microenvironment, biomarkers therapeutic targets cancer.

Language: Английский

---

Association Among the Gut Microbiome, the Serum Metabolomic Profile and RNA m6A Methylation in Sepsis-Associated Encephalopathy

Frontiers in Genetics, Journal Year: 2022, Volume and Issue: 13

Published: March 30, 2022

Objective: To investigate the relationship among gut microbiome, serum metabolomic profile and RNA m6A methylation in patients with sepsis-associated encephalopathy (SAE), 16S rDNA technology, metabolomics gene expression validation were applied. Methods: Serum feces collected from without (SAE group non-SAE group, respectively, n = 20). The of markers IL-6 was detected by enzyme-linked immunosorbent assay (ELISA), blood clinical indicators using a double antibody sandwich immunochemiluminescence method. regulator checked Q-RTPCR. microbiome analyzed sequencing metabolite revealed liquid chromatography-mass spectrometry (LC-MS/MS). Results: In SAE IL-6, ICAM-5 METTL3 levels significantly more than those while FTO decreased group. diversity as characterized profound increase commensals Acinetobacter, Methanobrevibacter, Syner-01 genera, decrease [Eubacterium]_hallii_group, depletion opportunistic organisms Anaerofilum, Catenibacterium, Senegalimassilia genera observed both groups. abundance Acinetobacter positively correlated METTL3. changes between intestinal flora showed significant correlation. Sphingorhabdus negatively 2-ketobutyric acid, 9-decenoic l-leucine, Glycyl-Valine [Eubacterium]_hallii_group 2-methoxy-3-methylpyazine, acetaminophen, synephrine acetonide. Conclusion: microbiota decreased. metabolites regulators PBMC changed compared to results that fecal biomarkers could be used for screening.

Language: Английский

---

N6-methyladenosine (m6A) writer KIAA1429 accelerates gastric cancer oxaliplatin chemoresistance by targeting FOXM1

Journal of Cancer Research and Clinical Oncology, Journal Year: 2022, Volume and Issue: 149(8), P. 5037 - 5045

Published: Nov. 3, 2022

Language: Английский

---

Molecular characterization of colorectal mucinous adenocarcinoma and adenocarcinoma, not otherwise specified, identified by multiomic data analysis

Frontiers in Molecular Biosciences, Journal Year: 2023, Volume and Issue: 10

Published: April 5, 2023

Adenocarcinoma not otherwise specified (AC) and mucinous adenocarcinoma (MC) have different biological behaviors clinical features. We utilized our previous proteomic data public transcriptome, single-cell spatial transcriptome databases to profile the molecular atlas of tumor microenvironments MC, AC, normal colon tissues. By exploring general specific features AC we found that was immune-active but exposed a hypoxic microenvironment. MC cells could protect against DNA damage, microenvironment unfavorable leukocyte transendothelial migration. identified several potential cellular targets for future research. also highlighted major difference between variety cell types functions possibly interactions. Stromal epithelial interactions play important roles in both regulatory pathways were involved.

Language: Английский

---

[Comprehensive Analysis of the Relationship between m6A Methylation Patterns and Immune Microenvironment in Lung Adenocarcinoma].

PubMed, Journal Year: 2022, Volume and Issue: 25(5), P. 311 - 322

Published: May 20, 2022

m6A RNA methylation modification plays an important role in the occurrence and progression of lung cancer regulates tumor immunity. Current studies mostly focus on differential expression some specific effectors infiltrating immune cell. is result mutual adjustment balance between effectors, changes one or two are far from enough to reflect panorama methylation. The microenvironment adenocarcinoma (LUAD) still poorly understood. aim this study investigate effect different patterns LUAD.LUAD data was obtained Cancer Genome Atlas (TCGA), University California Santa Cruz Xena (UCSC Xena) Gene Expression Omnibus (GEO) databases. mutation, survival analysis were performed for 24 effectors. pattern constructed by unsupervised clustering method, clusters analysis, gene set variation score cell infiltration performed. association LRPPRC protein levels CD8+ cytotoxic T lymphocytes CD68+ macrophages validated immunohistochemistry LUAD tissue microarray with 68 cases.The mutations effector found 150 567 cases a frequency 26.46%. 6 readers 3 writers significantly up regulated tissues compared normal tissues. IGF2BP1 HNRNPC independent risk factors prognosis LUAD. Abundant cross-talks among writers, erasers demonstrated. Three characteristics clinical established. Among be inversely associated macrophages, tissues.m6A play non-negligible roles regulating microenvironment. has potential new biomarker checkpoint inhibitor immunotherapy.【中文题目：肺腺癌中m6A RNA甲基化修饰特征 与免疫微环境相关性分析】 【中文摘要：背景与目的 RNA甲基化修饰在肺癌的发生与进展中起着重要作用，可以调节肿瘤免疫进而影响疾病预后。目前很多集中在某些特定的m6A效应器的差异表达及对肿瘤免疫细胞浸润的影响，但单个效应器表达的变化远远不足以反映m6A修饰特征的全貌，且关于m6A修饰对肺腺癌免疫微环境影响的研究仍较少。本研究拟探讨不同m6A修饰模式对肺腺癌中免疫微环境的影响。方法 从癌症基因组图谱数据库（The Atlas, TCGA）、加州大学圣克鲁兹分校泛癌全基因数据分析工具数据库（University Xena, UCSC Xena）、基因表达综合数据库（Gene Omnibus, GEO）获取肺腺癌相关数据信息。使用Maftools R分析肺腺癌队列中24个m6A效应器的基因突变，比较肺腺癌组织和正常组织中m6A效应器的表达差异，并通过Cox回归分析进行生存分析。通过Consensus Cluster Plus R非监督聚类的方法构建m6A修饰模式，进行m6A聚类生存分析、GSVA通路富集分析、免疫评分及免疫细胞浸润分析。在68例肺腺癌组织中，通过免疫组化分析LRPPRC蛋白表达水平与CD8、CD68的表达水平，验证LRPPRC与CD8+细胞毒性T细胞及巨噬细胞浸润的关系。结果 在567例肺腺癌样本中有150例发生了m6A效应器突变，频率为26.46%。与正常组织相比，肺腺癌组织中共有6个读取器和3个写入器的表达明显上调。IGF2BP1和HNRNPC是影响肺腺癌患者预后的独立危险因素，且各效应器之间也存在大量的相互作用。构建了3种具有不同免疫细胞浸润特征和临床预后的m6A修饰模式。发现LRPPRC的表达与包括杀伤性T细胞和巨噬细胞在内的多种免疫细胞的浸润呈负相关，并在68例肺腺癌组织中得到验证。结论 修饰对肺腺癌免疫微环境的调节起着重要作用，LRPPRC有可能作为预测抗PD1免疫治疗效果的潜在生物标记物。】 【中文关键词：肺腺癌；m6A修饰；免疫微环境；LRPPRC】.

Language: Английский

---