RBM15-dependent m6A modification mediates progression of non-small cell lung cancer cells DOI Creative Commons
Man Wang,

Ya‐Zhen Qin,

Xiaoqi Ai

et al.

Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(1)

Published: Dec. 23, 2024

Non-small cell lung cancer (NSCLC) is the predominant form of cancer, contributing significantly to global health and economic challenges. This study elucidated role RBM15 in NSCLC progression through its involvement m6A modifications. levels tissues cells were assessed via RT-qPCR Western blotting. The impact knockdown on proliferation, invasion, migration was evaluated using CCK-8, colony formation, Transwell assays. Expression KLF1, TRIM13, ANXA8 determined by blot. methylation analyzed, while RIP MeRIP assays employed explore interaction between YTHDF1/YTHDF2/m6A KLF1/TRIM13, as well KLF1 binding promoter. ubiquitination examined Xenograft metastasis models utilized assess RBM15's vivo. found be overexpressed NSCLC. Silencing led decreased cells. upregulated downregulated TRIM13 YTHDF1/YTHDF2, resulting promotion expression. overexpression or downregulation partially reversed suppressive effects proliferation. ANXA8, NSCLC, mitigated inhibitory silencing malignant behaviors. In vivo, hindered proliferation modulating KLF1-TRIM13/ANXA8 axis. RBM15-mediated enhances expression suppresses thereby promoting facilitating progression. These findings provide novel insights potential therapeutic targets for treatment.

Language: Английский

N6‐methyladenosine‐modified DBT alleviates lipid accumulation and inhibits tumor progression in clear cell renal cell carcinoma through the ANXA2/YAP axis‐regulated Hippo pathway DOI Creative Commons

Daojia Miao,

Qi Wang, Jian Shi

et al.

Cancer Communications, Journal Year: 2023, Volume and Issue: 43(4), P. 480 - 502

Published: March 1, 2023

The mechanism of metabolism reprogramming is an unsolved problem in clear cell renal carcinoma (ccRCC). Recently, it was discovered that the Hippo pathway altered tumor and promoted progression. Thus, this study aimed at identifying key regulators ccRCC pinpointing potential therapeutic targets for patients.Hippo-related gene sets metabolic were used to screen ccRCC. Public databases samples from patients applied investigate association dihydrolipoamide branched chain transacylase E2 (DBT) with signaling. role DBT confirmed by gain or loss function assays vitro vivo. Mechanistic results yielded luciferase reporter assay, immunoprecipitation, mass spectroscopy, mutational studies.DBT as a Hippo-related marker significant prognostic predictive value, its downregulation caused methyltransferase-like-3 (METTL3)-mediated N6-methyladenosine (m6 A) modification Functional studies specified suppressor inhibiting progression correcting lipid disorder findings revealed annexin A2 (ANXA2) interacted lipoyl-binding domain activate signaling which led decreased nuclear localization yes1-associated transcriptional regulator (YAP) repression lipogenic genes.This demonstrated tumor-suppressive DBT/ANXA2/YAP axis-regulated suggested target pharmaceutical intervention

Language: Английский

Citations

24
Targeting Hippo signaling in cancer: novel perspectives and therapeutic potential DOI Creative Commons

Liemei Lv,

Xiangxiang Zhou

MedComm, Journal Year: 2023, Volume and Issue: 4(5)

Published: Oct. 1, 2023

As highly conserved among diverse species, Hippo signaling pathway regulates various biological processes, including development, cell proliferation, stem function, tissue regeneration, homeostasis, and organ size. Studies in the last two decades have provided a good framework for how these fundamental functions of are tightly regulated by network with numerous intracellular extracellular factors. The pathway, when dysregulated, may lead to wide variety diseases, especially cancer. There is growing evidence demonstrating that dysregulated closely associated tumorigenesis, cancer invasion, migration, as well drug resistance. Therefore, considered an appealing therapeutic target treatment Promising novel agents targeting cancers recently emerged. These shown antitumor activity multiple models demonstrated potential treatment. However, detailed molecular basis signaling-driven tumor biology remains undefined. Our review summarizes current advances understanding mechanisms which drives tumorigenesis confers We also propose strategies future preclinical clinical development this pathway.

Language: Английский

Citations

24
Comprehensive bioinformatics analysis reveals the role of cuproptosis-related gene Ube2d3 in myocardial infarction DOI Creative Commons
Ming Yang, Yucheng Wang,

Liming He

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 19, 2024

Background Myocardial infarction (MI) caused by severe coronary artery disease has high incidence and mortality rates, making its prevention treatment a central challenging aspect of clinical work for cardiovascular practitioners. Recently, researchers have turned their attention to novel mechanism cell death Cu 2+ , cuproptosis. Methods This study integrated data from three MI-related bulk datasets downloaded the Gene Expression Omnibus (GEO) database, identified 16 differentially expressed genes (DEGs) related cuproptosis taking intersection 6378 DEGs obtained differential analysis with 49 cuproptosis-related genes. Four hub genes, Dbt, Dlat, Ube2d1 Ube2d3, were screened out through random forest Lasso analysis. In group, showed low expression, while Ube2d3 exhibited expression. Results Focusing on subsequent functional studies, we confirmed expression in MI group qRT-PCR Western Blot detection after successful construction mouse model left anterior descending (LAD) ligation, further clarified correlation development detecting levels proteins. Moreover, vitro experiments, was be highly oxygen-glucose deprivation (OGD)-treated cardiomyocytes AC16. order clarify role knocked down OGD-treated AC16 cells, Ube2d3’s promoting hypoxia damage cells inducing cuproptosis, as evidenced MTT, TUNEL, LDH release Conclusion summary, our findings indicate that regulates affect progression MI.

Language: Английский

Citations

13
CircMAST1 inhibits cervical cancer progression by hindering the N4-acetylcytidine modification of YAP mRNA DOI Creative Commons
Chunyu Zhang, Yuan Li,

Qiaojian Zou

et al.

Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)

Published: Feb. 8, 2024

Abstract Background Cervical cancer (CCa) is the fourth most common among females, with high incidence and mortality rates. Circular RNAs (circRNAs) are key regulators of various biological processes in cancer. However, role circRNAs cervical remains largely unknown. This study aimed to elucidate circMAST1 CCa. Methods CircRNAs related CCa progression were identified via a circRNA microarray. The relationship between levels clinicopathological features was evaluated using clinical specimens data 131 patients In vivo vitro experiments, including xenograft animal models, cell proliferation assay, transwell RNA pull-down whole-transcriptome sequencing, RIP RNA-FISH, performed investigate effects on malignant behavior Results CircMAST1 significantly downregulated tissues, low expression correlated poor prognosis. Moreover, our results demonstrated that inhibited tumor growth lymph node metastasis Mechanistically, competitively sequestered N-acetyltransferase 10 (NAT10) hindered Yes-associated protein (YAP) mRNA ac4C modification promote its degradation inhibit Conclusions plays major suppressive particular, can serve as potential biomarker novel target for

Language: Английский

Citations

4
Research progress of the Hippo signaling pathway in renal cell carcinoma DOI Creative Commons

Yiren Yang,

Xinxin Gan,

Wei Zhang

et al.

Asian journal of urology, Journal Year: 2024, Volume and Issue: 11(4), P. 511 - 520

Published: Feb. 11, 2024

This review aimed to summarize the role of Hippo signaling pathway in renal cell carcinoma (RCC), a urologic malignancy with subtle initial symptoms and high mortality rates due metastatic RCC (mRCC). The pathway, which regulates tissue organ size, plays crucial progression metastasis. Understanding involvement provides valuable insights for development targeted therapies improved patient outcomes. In this review, we explored impact on RCC. Through an analysis existing literature, examined its Additionally, discussed potential therapeutic strategies targeting inhibiting growth invasion. We also highlighted importance investigating interactions between other pathways such as Wnt, transforming factor-beta, PI3K/AKT, may uncover additional targets. has shown promise target Studies have demonstrated dysregulation RCC, altered expression key components YAP/TAZ. Targeting been associated suppressed tumor metastasis preclinical models Furthermore, crosstalk revealed synergistic effects that could be exploited interventions. is paramount importance. Elucidating functions molecular contributes diagnosis, treatment, discovery novel mechanisms. knowledge informs innovative opens new avenues research Further investigations are warranted fully comprehend complex interplay pathways, ultimately leading outcomes patients.

Language: Английский

Citations

4
Metabolic heterogeneity in tumor microenvironment – A novel landmark for immunotherapy DOI
Chen Chen, Peng Han, Yanping Qing

et al.

Autoimmunity Reviews, Journal Year: 2024, Volume and Issue: 23(6), P. 103579 - 103579

Published: June 1, 2024

Language: Английский

Citations

4
GPR137-RAB8A activation promotes ovarian cancer development via the Hedgehog pathway DOI Creative Commons
Chao Tang, Lin Li,

Chongying Zhu

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: Jan. 24, 2025

Language: Английский

Citations

0
Cuproptosis-related gene ACAD8 inhibits the metastatic ability of colorectal cancer by inducing cuproptosis DOI Creative Commons

HuiE Zhuang,

Yizhen Chen,

Sifu Huang

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 3, 2025

Background Distant metastasis of colorectal cancer (CRC) significantly impacts patient prognosis. Cuproptosis is a new form copper ion-dependent cell death. However, whether cuproptosis-related genes (CRGs) play role in the metastatic potential CRC remains unclear. This study focuses on CRGs-ACAD8 to explore its and mechanism (mCRC). Methods Clinical sample data from TCGA, GEO, Fujian Provincial Hospital patients were integrated analyze ACAD8 expression association with diagnosis prognosis CRC. Small interfering RNA, immunohistochemistry, colony formation, wound-healing assays so used evaluate biological functions ACAD8. Bioinformatics was applied investigate relationships immune infiltration, chemotherapy sensitivity, signaling pathways. Results reduced mCRC demonstrated excellent diagnostic performance. Patients high had better survival. closely associated enhanced sensitivity. Pathway enrichment analysis suggested that might inhibit by regulating pathways such as response metal ions tight junction organization. Finally, experiments confirmed positive correlation between levels mRNA expression, CuCl 2 upregulating expression. Knockdown induced cuproptosis. inhibited proliferation, stemness, migratory abilities cells, while si attenuated these effects. Moreover, sensitivity cells oxaliplatin 5-fluorouracil, whereas diminished this chemosensitizing effect. Conclusion As novel tumor suppressor, low holds prognostic value may contribute precise treatment infiltration

Language: Английский

Citations

0
Methyltransferase-like 3 is a target for the diagnose and therapy of clear cell renal carcinoma DOI Creative Commons
Dongqiong Xiao, Xiaojuan Su

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 17, 2025

Patients diagnosed with clear cell renal carcinoma (ccRCC) frequently exhibit metastatic disease, which complicates treatment strategies, underscoring the urgent need for mechanistic insights and early diagnostic biomarkers. Current research is dedicated to uncovering mechanisms behind ccRCC development resistance treatment, a particular focus on role of methyltransferase-like 3 (METTL3) in RNA N6-methyladenosine modification, key gene regulatory process. This review synthesizes current evidence METTL3's functions, revealing its oncogenic activity through m6A-mediated regulation stability translation, promotes tumor progression, metastasis, chemoresistance. We further explore dual therapeutic relevance, including utility as prognostic biomarker targeting via novel strategies such small-molecule inhibitors (e.g., Erianin) combination therapies mTOR or immune checkpoint inhibitors. By consolidating these advances, this positions METTL3 critical node advancing precision medicine ccRCC.

Language: Английский

Citations

0
Epitranscriptomic Role of m6A in Obesity-Associated Disorders and Cancer Metabolic Reprogramming DOI Open Access
Sujun Yan, Weiping Wen, Zhe Mo

et al.

Genes, Journal Year: 2025, Volume and Issue: 16(5), P. 498 - 498

Published: April 27, 2025

The global rise in obesity and its associated metabolic disorders underscores the need for a deeper investigation into their underlying molecular mechanisms. While genetic factors are well-established contributors, recent research has increasingly focused on epigenetic regulators, particularly N6-methyladenosine (m6A)—the most prevalent internal RNA modification eukaryotes. This post-transcriptional plays crucial role metabolism by regulating mRNA stability, splicing, nuclear export, translation efficiency. Notably, emerging evidence implicates m6A both adipogenesis dysregulation. In this review, we systematically examine three key dimensions: (1) mechanisms of modification, including writers, erasers, readers, obesity; (2) dysregulated patterns obesity-related pathologies, such as type 2 diabetes (T2D), insulin resistance, dysfunction-associated steatotic liver disease (MASLD), glycolysis cancer cells; (3) therapeutic potential targeting regulators. By critically assessing advancements, highlight m6A’s dual sensor modulator, offering novel insights strategies combating syndromes.

Language: Английский

Citations

0