N6‐methyladenosine reader hnRNPA2B1 recognizes and stabilizes NEAT1 to confer chemoresistance in gastric cancer

Cancer Communications, Год журнала: 2024, Номер 44(4), С. 469 - 490

Опубликована: Март 21, 2024

Abstract Background Chemoresistance is a major cause of treatment failure in gastric cancer (GC). Heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) an N6‐methyladenosine (m 6 A)‐binding protein involved variety cancers. However, whether m A modification and hnRNPA2B1 play role GC chemoresistance largely unknown. In this study, we aimed to investigate the downstream mechanism chemoresistance. Methods The expression among public datasets were analyzed validated by quantitative PCR (qPCR), Western blotting, immunofluorescence, immunohistochemical staining. biological functions investigated both vitro vivo. RNA sequencing, methylated immunoprecipitation, stability assay performed assess association between binding RNA. maintenance stemness was evaluated bioinformatic analysis, qPCR, sphere formation assays. patterns regulators specimens from patients who received adjuvant chemotherapy RNAscope multiplex immunohistochemistry. Results Elevated found cells tissues, especially multidrug‐resistant (MDR) cell lines. associated with poor outcomes patients, those 5‐fluorouracil treatment. Silencing effectively sensitized inhibiting proliferation inducing apoptosis Mechanically, interacted stabilized long noncoding NEAT1 A‐dependent manner. Furthermore, worked together enhance properties via Wnt/β‐catenin signaling pathway. clinical subjected chemotherapy, levels hnRNPA2B1, NEAT1, CD133, CD44 markedly elevated non‐responders compared responders. Conclusion Our findings indicated that interacts stabilizes lncRNA which contribute property pathway exacerbate GC.

Язык: Английский

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Writers, readers, and erasers RNA modifications and drug resistance in cancer

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Авг. 30, 2024

Drug resistance in cancer cells significantly diminishes treatment efficacy, leading to recurrence and metastasis. A critical factor contributing this is the epigenetic alteration of gene expression via RNA modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G), pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing. These modifications are pivotal regulating splicing, translation, transport, degradation, stability. Governed by "writers," "readers," "erasers," impact numerous biological processes progression, including cell proliferation, stemness, autophagy, invasion, apoptosis. Aberrant can lead drug adverse outcomes various cancers. Thus, targeting modification regulators offers a promising strategy for overcoming enhancing efficacy. This review consolidates recent research on role prevalent resistance, with focus m6A, m1A, m5C, m7G, Ψ, A-to-I Additionally, it examines regulatory mechanisms linked underscores existing limitations field.

Язык: Английский

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Nanomaterials in gastric cancer: pioneering precision medicine for diagnosis, therapy, and prevention

Medical Oncology, Год журнала: 2025, Номер 42(4)

Опубликована: Март 6, 2025

Язык: Английский

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Exploring m6A modifications in gastric cancer: from molecular mechanisms to clinical applications

European journal of medical research, Год журнала: 2025, Номер 30(1)

Опубликована: Фев. 12, 2025

The significance of m6A modifications in several biological processes has been increasingly recognized, particularly the context cancer. For instance, gastric cancer (GC) have significantly implicated tumor progression, metastasis, and treatment resistance. GC is characterized by differential expression regulators. High writers such as METTL3 WTAP are associated with poor prognosis aggressive clinical features. Conversely, low METTL14 linked to worse outcomes, whereas elevated levels demethylases, FTO ALKBH5, correlate better survival rates. These regulators influence cellular functions, including proliferation, invasion, migration, glycolysis, chemotherapy resistance, thereby affecting growth therapeutic outcomes. assessment modification patterns profiles m6A-related genes hold substantial potential for improving diagnosis GC. In this review, we provide an updated comprehensive summary role GC, emphasizing their molecular mechanisms, significance, translational applications developing novel diagnostic strategies.

Язык: Английский

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Mechanistic insights into HNRNPA2B1: A comprehensive pan-cancer analysis and functional characterization in lung cancer

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2025, Номер unknown, С. 167669 - 167669

Опубликована: Янв. 1, 2025

Язык: Английский

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FOSL1 drives the malignant progression of pancreatic cancer cells by regulating cell stemness, metastasis and multidrug efflux system

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Март 4, 2025

Targeted therapy is an effective strategy for the treatment of advanced and metastatic pancreatic cancer, one leading causes cancer-related death worldwide. To address limitations existing targeted drugs, there urgently need to find novel targets therapeutic strategies. Transcription factor FOS like 1 (FOSL1) a potential target challenging which contributes malignant progression poor gnosis cancer. High mobility group A1 (HMGA1) nonhistone chromatin structural protein that prognosis Human FOSL1 complete RNA, shRNA against HMGA1 lentiviral recombination vectors were used overexpress knock down HMGA1. RNA sequencing, Q-PCR Western blots investigate mechanism in regulating proliferation cancer cells. The relationship between analyzed by co-immunoprecipitation Mass spectrometry, immunoprecipitation blots. regulation invasion migration, stemness, multidrug efflux system determined transwell assay, sphere formation immunofluorescence, We found promoted trigging metastasis, drug resistance. was key downstream regulated at transcriptional level directly interacted with FOSL1. Knockdown inhibited cells expression genes related epithelial-mesenchymal transition system. inhibition significantly promote promoting expression. Targeting monotherapy or combination promising metastasis

Язык: Английский

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LncRNA in gastric cancer drug resistance: deciphering the therapeutic strategies

Frontiers in Oncology, Год журнала: 2025, Номер 15

Опубликована: Апрель 1, 2025

Gastric cancer (GC) is an exceedingly aggressive disease and ranks as the third leading cause of cancer-related deaths, which poses a huge health burden globally. Chemotherapy commonly employed during middle to advanced stages cancer, although it faces frequent treatment failures attributed drug resistance. Thus, imperative for researchers identify potential targets overcoming therapeutic resistance, thereby facilitating development novel anti-cancer agents GC patients with stages. Long noncoding RNAs (lncRNAs) are diverse group transcripts limited protein-coding capacity, have been recognized functional molecules regulating progression including cell proliferation, metastasis, resistance in GC. In this review, we examine intricate molecular networks on role lncRNAs LncRNAs conferred through various mechanisms, therefore functioning promising patients. Additionally, discuss current advancements strategies targeting therapy, may pave way lncRNA-mediated precision medicine malignant disease.

Язык: Английский

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Peptides based on the interface of hnRNPA2B1-transthyretin complex repress retinal angiogenesis in diabetic retinopathy

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Апрель 19, 2025

Heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) plays a vital role in angiogenesis, when its nucleic acid-binding domain is occupied by transthyretin (TTR), the neovascularization of human retinal microvascular endothelial cells (hRECs) repressed under hyperglycemic conditions. HnRNPA2B1-targeting peptides (THIPs) were designed based on core fragments at TTR-hnRNPA2B1 interface. Biacore, Langmuir equilibrium adsorption, and co-immunoprecipitation (co-IP) assays performed to determine association between THIPs hnRNPA2B1. Proliferation DNA synthesis hRECs detected using CCK-8 EdU assays. Transwell, wound healing, tube formation used evaluate migratory angiogenic capacity hRECs. Related RNA protein expression levels tested quantitative PCR western blot assays, respectively. Streptozotocin (STZ)-induced diabetic retinopathy (DR) model rats intravitreally injected with 5 μL AAV9 virus (1 × 1012 vg/mL) every 8 weeks, sterile saline as control. After 16 retinas extracted subjected Evans blue leakage trypsin digestion Retinal paraffin sections prepared stained hematoxylin eosin (H&E) or immunohistochemical immunofluorescence co-IP analyses demonstrated that four specifically recognized labeling showed inhibited proliferation hyperglycemia. healing Quantitative suggested exerted their effects via STAT4/miR-223-3p/FBXW7 downstream Notch1/Akt/mTOR axes. In vivo studies DR rat revealed intravitreal administration THIP-4 significantly mitigated leakage, capillary decellularization, pericyte loss, fibrosis, gliosis during progression. Our findings hyperglycemia, suppressed progression axes both vitro vivo. These results indicated has strong potential for clinical application other angiogenesis associated diseases.

Язык: Английский

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Research progress on m6A and drug resistance in gastrointestinal tumors

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Апрель 28, 2025

Gastrointestinal (GI) tumors represent a significant global health burden and are among the leading causes of cancer-related mortality worldwide. their drug resistance is one major challenges in cancer therapy. In recent years, epigenetic modifications, especially N6-methyladenosine (m6A) RNA have become hot research topic. m6A modification plays an important role gene expression progression by regulating splicing, translation, stability, degradation, which regulated "writers," "erasers" "readers." GI tumors, to chemotherapy, targeted therapy, immunotherapy closely associated with modification. Therefore, molecular mechanism its development provide new therapeutic strategies for overcoming efficacy tumors. this review, biological functions were explored, specific mechanisms different types ideas targets future treatment identified, limitations field highlighted.

Язык: Английский

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Prognosis and Biological Function of CYB5R Family in Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma: A Multi-omics Analysis

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Апрель 28, 2025

The cytochrome b5 reductase (CYB5R) family of enzymes, consisting five members, has been reported to profoundly affect various physiological and pathological processes. However, it remains unclear how CYB5Rs function have prognostic value in cervical squamous cell carcinoma endocervical adenocarcinoma (CESC). In this study. Gene expression data clinical details 304 CESC patients were acquired from Cancer Genome Atlas (TCGA) database. Data processing visualization conducted using a range databases R programs, such as GEPIA, GeneMANIA, MethSurv, GSCA, starBase. tumor tissues, the mRNA levels CYB5R1 CYB5R4 increased, while those CYB5R2 CYB5R3 decreased. Elevated correlated with adverse outcomes diagnosed CESC. was negatively Stromal Score, Immune ESTIMATE Scor addition, significantly associated NK cells GO KEGG enrichment analyses indicated that genes related are pathways including extracellular matrix (ECM) receiver interaction, cycle, ubiquitin-mediated proteolysis. Molecular mechanisms may play role tumorigenesis progression

Язык: Английский

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