The oncofetal protein IMP1 regulates the transcriptomic landscape to drive early events in pancreatic cancer progression and growth DOI

Orçun Haçarız,

Julia Messina‐Pacheco,

Elliot Goodfellow

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 2, 2024

ABSTRACT Background & Aims Pancreatic ductal adenocarcinoma (PDAC) has a dismal 5-year survival rate of 12% - the lowest all malignancies. This is partially due to late diagnosis, as early stages disease, including process acinar metaplasia (ADM) are not presently detectable. Insulin-like growth factor 2 mRNA binding protein (IMP)1 an oncofetal implicated in cancer progression. Here, we aimed determine its role PDAC development and maintenance malignant phenotype. Methods IMP1 expression was analyzed surgical specimens pancreatic tissue derived from KPC mice. Murine organoids expressing Kras G12D mutant were treated with inhibitor BTYNB RNAseq performed. The function targets ADM model effect silencing on cells evaluated vivo . Results We found high precancerous lesions human murine PDAC, but normal pancreas. Blockade impeded organoid profoundly altered transcriptional landscape organoids, reducing cytokine-cytokine receptor interactors, cell adhesion invasion mediators such Card11, Gkn3 , Il13ra2 Mmp9 Vcam1 Gastrokine-3 IL-13 turn, enhanced process. Finally, inhibited their metastatic outgrowth Conclusions master regulator events progression potential biomarker target for this disease.

Language: Английский

A pan-cancer analysis reveals the oncogenic and immunological role of insulin-like growth factor 2 mRNA-binding protein family members DOI Creative Commons
Fangfang Zeng, Liuyan Chen, Jing Li

et al.

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 15, 2025

Abstract Purpose To investigate the expression and clinical significance of insulin-like growth factor 2 mRNA-binding protein family members (IGF2BPs) in pan-cancer evaluate their potential as targets for tumor immunotherapy. Methods Based on data from cancer genome atlas (TCGA) database, analysis was conducted to examine IGF2BPs twenty-two tumors. Results Differential showed high most tissues. Survival mutation analyses suggested that overexpression associated with poor prognosis status certain Methylation revealed methylation levels IGF2BP1/2/3 tumors were intricately linked mRNA expression, patient prognosis, immune cell infiltration. Enrichment indicated abnormal various common tumor-related pathways different tumors, including AMPK, Hippo, PI3K-Akt, EMT, p53. In addition, correlation closely related immunotherapy-related indicators (immune infiltration, major histocompatibility complex (MHC), checkpoints, burden (TMB), microsatellite instability (MSI)) some Drug sensitivity sensitive chemotherapeutic drugs (alvocidib, dasatinib, trametinib, selumetinib). Conclusion exhibit significantly are pathological stage, mutational status, levels, relevant immunotherapy multiple Moreover, may play an oncogenic role by activating signaling pathways. Therefore, be prognostic markers therapy drug therapy.

Language: Английский

Citations

1
IGF2BP3-stabilized CAMK1 regulates the mitochondrial dynamics of renal tubule to alleviate diabetic nephropathy DOI Creative Commons

Yuan Du,

Hao Li,

Wenni Dai

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2024, Volume and Issue: 1870(3), P. 167022 - 167022

Published: Jan. 11, 2024

Language: Английский

Citations

6
Insights into the m6A demethylases FTO and ALKBH5 : structural, biological function, and inhibitor development DOI Creative Commons

Zewei Gao,

Xuan Zha,

Min Li

et al.

Cell & Bioscience, Journal Year: 2024, Volume and Issue: 14(1)

Published: Aug. 27, 2024

Abstract N6-methyladenosine (m 6 A) is dynamically regulated by methyltransferases (termed “writers”) and demethylases (referred to as “erasers”), facilitating a reversible modulation. Changes in m A levels significantly influence cellular functions, such RNA export from the nucleus, mRNA metabolism, protein synthesis, splicing. They are intricately associated with spectrum of pathologies. Moreover, dysregulation modulation has emerged promising therapeutic target across many diseases. plays pivotal role controlling vital downstream molecules critical biological pathways, contributing pathogenesis evolution numerous conditions. This review provides an overview demethylases, explicitly detailing structural functional characteristics FTO ALKBH5. Additionally, we explore their distinct involvement various diseases, examine factors regulating expression, discuss progress inhibitor development.

Language: Английский

Citations

6
Targeting insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) for the treatment of cancer DOI

Yuanqian Cai,

Yingzhe Wang, Bingjie Mao

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 268, P. 116241 - 116241

Published: Feb. 15, 2024

Language: Английский

Citations

5
Paeoniflorin increases the anti-tumor efficacy of sorafenib in tumor-bearing mice with liver cancer via suppressing the NF-κb/PD-l1 axis DOI Creative Commons
J. Li,

Chenghui Zhu,

Zengyu Zhang

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(2), P. e24461 - e24461

Published: Jan. 1, 2024

BackgroundSorafenib (Sor) represents a first-line therapy for hepatocellular carcinoma (HCC); however, its efficacy is constrained by secondary failure, which limits clinical use. Recent studies have indicated that the suppression of Programmed cell death-Ligand 1 (PD-L1) may potentiate Sor's anti-liver cancer effects; furthermore, PD-L1 expression known to be regulated NF-κB. Previous research has demonstrated paeoniflorin (PF) downregulates NF-κB axis, nevertheless, current not yet determined whether PF can synergistically enhance Sor against HCC modulating NF-κB/PD-L1 pathway.MethodsThe study employed H22 hepatoma-bearing mouse model, was treated with PF, Sor, and their combination over period 12 days. The impact on tumor growth, proliferation, apoptosis, T-cell subsets, IL-2 IFN-γ production, assessed. Moreover, Splenic lymphocyte from normal mice cells model were co-cultured in vitro, tumor-specific cytotoxic T activity analyzed. In final phase study, Huh-7 stimulated an activator or inhibitor, subsequent production investigated.ResultsPF exhibit synergistic anti-tumor effect, compared use alone, combined significantly increased number CD4+ CD8+ tissue, markedly enhanced lymphocytes, reversed depletion interleukin-2 increase following intervention. This also further reduced level peripheral blood tissue. Additionally, vitro experiments confirmed reduces liver inhibiting NF-κB.ConclusionsPF plays role progression regulating pathway.

Language: Английский

Citations

4
Targeting RNA modifications with pharmacological agents: New frontiers in cancer therapy DOI Creative Commons
Angel Guan, Justin Wong

Cancer Medicine, Journal Year: 2024, Volume and Issue: 13(7)

Published: March 28, 2024

Abstract The N6‐methyladenosine (m6A) RNA modification has gained significant prominence as a new layer of regulatory mechanism that governs gene expression. Over the past decade, various m6A regulators responsible for introducing, eliminating, and recognising methylation have been identified. Notably, these often exhibit altered expression patterns in cancer, occasionally offering prognostic value. Nonetheless, complex roles human cancer pathology remain enigmatic, with conflicting outcomes reported different studies.In recent years, multitude inhibitors activators targeting reported. Several compounds demonstrated promising efficacy both vitro vivo models. These findings collectively underscore dynamic landscape regulation biology, revealing its potential therapeutic target indicator.

Language: Английский

Citations

4
Multifaceted roles of insulin‑like growth factor 2 mRNA binding protein 2 in human cancer (Review) DOI Creative Commons

Jianan Shen,

Youxiang Ding

Molecular Medicine Reports, Journal Year: 2025, Volume and Issue: 31(3)

Published: Jan. 24, 2025

Insulin‑like growth factor 2 mRNA binding protein (IGF2BP2) is an RNA that functions as N6‑methyladenosine reader. It regulates various biological processes in human cancers by affecting the stability and expression of target transcripts, including coding RNAs non‑coding (ncRNAs). Numerous studies have shown IGF2BP2 aberrantly increased types cancer plays multifaceted roles development progression cancers. In present review, clinical importance summarized its involvement regulation processes, proliferation, metastasis, chemoresistance, metabolism, tumor immunity, stemness cell death, discussed. The chemical compounds been developed inhibitors are also detailed. As ncRNAs now important potential therapeutic agents for treatment, microRNAs reported to directly inhibit described. summary, reviewing latest literature, study aimed highlight physiological cancer, with a focus on great inhibitor development. review may inspire new ideas future IGF2BP2, which serve specific cancer.

Language: Английский

Citations

0
The biological roles and molecular mechanisms of m6A reader IGF2BP1 in the hallmarks of cancer DOI Creative Commons

Qiu Li,

Shourong Wu, Lei Zhang

et al.

Genes & Diseases, Journal Year: 2025, Volume and Issue: unknown, P. 101567 - 101567

Published: Feb. 1, 2025

Language: Английский

Citations

0
RNA Modification in Metabolism DOI Creative Commons
Yadi Liu,

Zhongyan Sun,

Dingkun Gui

et al.

MedComm, Journal Year: 2025, Volume and Issue: 6(3)

Published: March 1, 2025

ABSTRACT Epigenetic regulation in disease development has been witnessed within this decade. RNA methylation is the predominant form of epigenetic regulation, and most prevalent modification N6‐methyladenosine (m 6 A). Recently, emerged as a potential target for treatment. posttranscriptional gene expression that involved both physiological pathological processes. Evidence suggests m A significantly affects metabolism, its abnormal changes have observed variety diseases. Metabolic diseases are series caused by metabolic processes body, common include diabetes mellitus, obesity, nonalcoholic fatty liver disease, etc.; although pathogenesis these differs from each other to current understanding, recent studies suggested pivotal role modulating diseases, A‐based drug on agenda. This paper reviewed understanding hoping provide systematic information those area.

Language: Английский

Citations

0
The impact of an RNA-binding protein group on regulating the RSPO-LGR4/5-ZNRF3/RNF43 module and the immune microenvironment in hepatocellular carcinoma DOI Creative Commons
Zhengyao Xie, Zhijun Dai, Ziyao Liu

et al.

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 22, 2025

Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality. RNA-binding proteins (RBPs) are potential therapeutic targets because their role in tumor progression. This study investigated the interactions between specific HCC progression-associated RBPs (HPARBPs), namely, ILF3, PTBP1, U2AF2, NCBP2, RPS3, and SSB, downstream targets, as well impact on immune microenvironment clinical value. Tissue samples from human HCC, collected 28 patients who experienced recurrence following postoperative adjuvant therapy were examined. The mRNA levels prospective quantified through RNA isolation quantitative real-time PCR. Data two public datasets scrutinized for both expression relevance. Through Student's t test logistic regression, HPARBPs identified. Enhanced cross-linking immunoprecipitation (eCLIP) experiments revealed RBP-RNA HepG2 cells. For functional enrichment, Metascape was used, whereas CIBERSORT used to characterize microenvironment. Public database analysis confirmed widespread RBP abnormalities (false discovery rate < 0.00001 fold change ≥ 1.15 or ≤ 0.85), identification 42 core modules. eCLIP data specificity target genes binding site features (signal value > 3, P 0.01). Four may bind RNAs RSPO-LGR4/5-ZNRF3/RNF43 module, affecting Wnt pathway Immunoinfiltration changes due altered relevant genes. In our study, we identified that might contribute progression by module. Changes affect Our findings offer novel insights into regulatory network pathway-related HCC.

Language: Английский

Citations

0