KIAA1429-mediated m6A modification of CHST11 promotes progression of diffuse large B-cell lymphoma by regulating Hippo–YAP pathway DOI Creative Commons
Xiaohong Chen,

Tiange Lu,

Yiqing Cai

et al.

Cellular & Molecular Biology Letters, Journal Year: 2023, Volume and Issue: 28(1)

Published: April 19, 2023

N6-methyladenosine (m6A) has been shown to participate in various essential biological processes by regulating the level of target genes. However, function m6A modification mediated KIAA1429 [alias virus-like methyltransferase-associated protein (VIRMA)] during progression diffuse large B-cell lymphoma (DLBCL) remains undefined.The expression and clinical significance were verified our data. CRISPR/Cas9 deletion, CRISPR/dCas9-VP64 for activating endogenous was used evaluate its function. RNA sequencing (RNA-seq), methylated immunoprecipitation (MeRIP-seq), (RIP) assays, luciferase activity assay, stability experiments, co-immunoprecipitation performed investigate regulatory mechanism DLBCL. Tumor xenograft models established vivo experiments.Dysregulated regulators observed, a novel predictive model based on score Additionally, elevated associated with poor prognosis patients Knockout repressed DLBCL cell proliferation, facilitated cycle arrest G2/M phase, induced apoptosis vitro, inhibited tumor growth vivo. Furthermore, carbohydrate sulfotransferase 11 (CHST11) identified as downstream KIAA1429, which CHST11 mRNA then recruited YTHDF2 reducing expression. Inhibition diminished MOB1B expression, resulting inactivation Hippo-YAP signaling, reprogramming Hippo genes.Our results revealed new pathway is inactivated KIAA1429/YTHDF2-coupled epitranscriptional repression CHST11, highlighting potential biomarker therapeutic progression.

Language: Английский

The role of m6A RNA methylation in cancer metabolism DOI Creative Commons
Yuanyuan An, Hua Duan

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Jan. 12, 2022

Abstract Metabolic reprogramming is one of the main characteristics malignant tumors, which due to flexible changes cell metabolism that can meet needs growth and maintain homeostasis tissue environments. Cancer cells obtain metabolic adaptation through a variety endogenous exogenous signaling pathways, not only promote cancer cells, but also start transformation process adapt tumor microenvironment. Studies show m6A RNA methylation widely involved in recombination cells. In eukaryotes, most abundant modification mRNA, almost all cycle stages, including regulation transcription, maturation, translation, degradation stability mRNA. M6A be physiological pathological processes, cancer. this review, we discuss role plays metabolism-related molecules aiming importance targeting regulating metabolism.

Language: Английский

Citations

483
m6A modification: recent advances, anticancer targeted drug discovery and beyond DOI Creative Commons
Lijuan Deng,

Wei-Qing Deng,

Shu-Ran Fan

et al.

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Feb. 14, 2022

Abstract Abnormal N6-methyladenosine (m6A) modification is closely associated with the occurrence, development, progression and prognosis of cancer, aberrant m6A regulators have been identified as novel anticancer drug targets. Both traditional medicine-related approaches modern discovery platforms used in an attempt to develop m6A-targeted drugs. Here, we provide update latest findings on critical roles cancer progression, summarize rational sources for agents from medicines computer-based chemosynthetic compounds. This review highlights potential targeting treatment proposes advantage artificial intelligence (AI) m6A-targeting Graphical abstract Three stages discovery: medicine-based natural products, chemical or synthesis, (AI)-assisted future.

Language: Английский

Citations

262
The roles and implications of RNA m6A modification in cancer DOI
Xiaolan Deng, Ying Qing, David Horne

et al.

Nature Reviews Clinical Oncology, Journal Year: 2023, Volume and Issue: 20(8), P. 507 - 526

Published: May 23, 2023

Language: Английский

Citations

179
Role of m6A writers, erasers and readers in cancer DOI Creative Commons
Zhen Fang,

Wentong Mei,

Chang Qu

et al.

Experimental Hematology and Oncology, Journal Year: 2022, Volume and Issue: 11(1)

Published: Aug. 9, 2022

Abstract The N(6)-methyladenosine (m6A) modification is the most pervasive of human RNAs. In recent years, an increasing number studies have suggested that m6A likely plays important roles in cancers. Many demonstrated involved biological functions cancer cells, such as proliferation, invasion, metastasis, and drug resistance. addition, closely related to prognosis patients. this review, we highlight advances understanding function various We emphasize importance progression look forward describe future research directions.

Language: Английский

Citations

148
Metabolic reprogramming and epigenetic modifications in cancer: from the impacts and mechanisms to the treatment potential DOI Creative Commons
Xuemeng Xu, Peng Qiu,

Xianjie Jiang

et al.

Experimental & Molecular Medicine, Journal Year: 2023, Volume and Issue: 55(7), P. 1357 - 1370

Published: July 3, 2023

Abstract Metabolic reprogramming and epigenetic modifications are hallmarks of cancer cells. In cells, metabolic pathway activity varies during tumorigenesis progression, indicating regulated plasticity. changes often closely related to changes, such as alterations in the expression or epigenetically modified enzymes, which may exert a direct an indirect influence on cellular metabolism. Therefore, exploring mechanisms underlying regulating tumor cell metabolism is important for further understanding pathogenesis. Here, we mainly focus latest studies regulations, including glucose, lipid amino acid context, then emphasize modifications. Specifically, discuss role played by DNA methylation, chromatin remodeling, noncoding RNAs histone lactylation growth progression. Finally, summarize prospects potential therapeutic strategies based

Language: Английский

Citations

99
Tumor associated macrophages-derived exosomes facilitate hepatocellular carcinoma malignance by transferring lncMMPA to tumor cells and activating glycolysis pathway DOI Creative Commons
Minghao Xu, Chenhao Zhou, Jialei Weng

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)

Published: Aug. 19, 2022

Tumor-associated macrophages (TAMs), which form a large part of the tumor microenvironment, are normally regulated by metabolic reprogramming. However, potential mechanisms immune-metabolism interaction between hepatocellular carcinoma (HCC) cells and TAMs remain unclear.The candidate long non-coding RNAs (lncRNAs) were screened Smart-seq based scRNA-seq method then validated qPCR. Immunostaining analysis was done to examine levels markers for glycolysis. Exosomes from primary human HCC tissues isolated centrifugation, their internalization with lncRNAs confirmed immunofluorescence. The underlying mechanism TAMs-derived exosomal lncRNA luciferase reporter assay RNA immunoprecipitation. Metabolism regulation evaluated through glucose consumption, lactate productions extracellular acidification rates (ECARs). Mouse xenograft models used elucidate in vivo effect on growth.TAMs augment aerobic glycolysis proliferation exosome transmission myeloid-derived lncRNA, M2 macrophage polarization associated (lncMMPA). Mechanistically, lncMMPA not only could polarize macrophage, but also act as an microRNA sponge interact miR-548 s increase mRNA level ALDH1A3, further promote metabolism cell HCC. Moreover, increased multiplication interacting vivo. Clinically, expression associates reduced survival patients.LncMMPA plays important role regulating malignancy reprogramming s/ALDH1A3 pathway.

Language: Английский

Citations

91
TRIM7 modulates NCOA4-mediated ferritinophagy and ferroptosis in glioblastoma cells DOI
Kaiqiang Li, Bingyu Chen,

Aibo Xu

et al.

Redox Biology, Journal Year: 2022, Volume and Issue: 56, P. 102451 - 102451

Published: Aug. 28, 2022

Language: Английский

Citations

84
m6A methylation: a process reshaping the tumour immune microenvironment and regulating immune evasion DOI Creative Commons
Xiaoxue Cao,

Qishun Geng,

Danping Fan

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: March 1, 2023

Abstract N6-methyladenosine (m 6 A) methylation is the most universal internal modification in eukaryotic mRNA. With elaborate functions executed by m A writers, erasers, and readers, modulation involved myriad physiological pathological processes. Extensive studies have demonstrated diverse tumours, with effects on tumorigenesis, metastasis, resistance. Recent evidence has revealed an emerging role of tumour immunoregulation, divergent patterns been microenvironment. To depict regulatory immune microenvironment (TIME) its effect evasion, this review focuses TIME, which characterized hypoxia, metabolic reprogramming, acidity, immunosuppression, outlines A-regulated TIME evasion under stimuli. Furthermore, anti-tumour cells are summarized.

Language: Английский

Citations

56
Small RNA modifications: regulatory molecules and potential applications DOI Creative Commons
Qunli Xiong, Yaguang Zhang

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: June 22, 2023

Abstract Small RNAs (also referred to as small noncoding RNAs, sncRNA) are defined polymeric ribonucleic acid molecules that less than 200 nucleotides in length and serve a variety of essential functions within cells. RNA species include microRNA (miRNA), PIWI-interacting (piRNA), interfering (siRNA), tRNA-derived (tsRNA), etc. Current evidence suggest can also have diverse modifications their nucleotide composition affect stability well capacity for nuclear export, these relevant drive molecular signaling processes biogenesis, cell proliferation differentiation. In this review, we highlight the characteristics cellular modifications, current techniques reliable detection. We discuss how may be clinical applications diagnosis treatment human health conditions such cancer.

Language: Английский

Citations

53
Targeting the Warburg effect: A revisited perspective from molecular mechanisms to traditional and innovative therapeutic strategies in cancer DOI Creative Commons

Minru Liao,

Dahong Yao,

Lifeng Wu

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 14(3), P. 953 - 1008

Published: Dec. 16, 2023

Cancer reprogramming is an important facilitator of cancer development and survival, with tumor cells exhibiting a preference for aerobic glycolysis beyond oxidative phosphorylation, even under sufficient oxygen supply condition. This metabolic alteration, known as the Warburg effect, serves significant indicator malignant transformation. The effect primarily impacts occurrence by influencing pathway in cells. Key enzymes involved this process include glucose transporters (GLUTs), HKs, PFKs, LDHs, PKM2. Moreover, expression transcriptional regulatory factors proteins, such FOXM1, p53, NF-

Language: Английский

Citations

53