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

Sep 21, 2026

Chemoresistance drives treatment failure in gastric cancer (GC), yet the contribution of N6-methyladenosine (m6A) signaling and hnRNPA2B1 remains unclear. This study analyzes public datasets and validates hnRNPA2B1 roles using qPCR, Western blotting, immunofluorescence, immunohistochemistry, and multiple RNA assays. Functional experiments in vitro and in vivo assess proliferation, apoptosis, stemness, and chemo-sensitivity. Results show hnRNPA2B1 upregulation in GC, especially multidrug-resistant lines, and linkage to poor outcomes under 5-fluorouracil.

LanguageEnglish

CategoryHealthcare

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Pages22

Reading Time55 min

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Background

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DOI: 10.1002/cac2.12534 ORIGINAL ARTICLE N6-methyladenosine reader hnRNPA2B1 recognizes and stabilizes NEAT1 to confer chemoresistance in gastric cancer Jiayao Wang1, 2 Yihan Zhao4 Daiming Fan1 Jiehao Zhang1,2 Hao Liu1 Lingnan Meng1, 3 Xianchun Gao1 Chen Wang5 Xiaoliang Gao1 Ahui Fan1 Tianyu Cao1 Xiaodi Zhao1 Yuanyuan Lu1 1 State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, Shaanxi, P. R. China 2The Air Force Hospital of Southern Theater Command, Guangzhou, Guangdong, P. R. China 3National Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Guangxi Medical University, Nanning, Guangxi, P. R. China 4 Second Clinical College, Shaanxi University of Traditional Chinese Medicine, Xianyang, Shaanxi, P. R. China 5 College of Life Sciences, Northwest University, Xi’an, Shaanxi, P. R. China Correspondence Yuanyuan Lu, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an 710032, Shaanxi, P. R. China. Email: [luyuandreamer@aliyun.com](luyuandreamer@aliyun.com). Xiaodi Zhao, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Abstract Background: Chemoresistance is a major cause of treatment failure in gastric cancer (GC). Heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) is an N6-methyladenosine (m6A)-binding protein involved in a variety of cancers. However, whether m6A modification and hnRNPA2B1 play a role in GC chemoresistance is largely unknown. In this study, we aimed to investigate the role of hnRNPA2B1 and the downstream mechanism in GC chemoresistance. Methods: The expression of hnRNPA2B1 among public datasets were analyzed and validated by quantitative PCR (qPCR), Western blotting, immunofluorescence, and immunohistochemical staining. The biological functions of List of Abbreviations: ADR, Adriamycin; ASO, antisense oligonucleotide; CCK-8, Cell Counting Kit-8; CLIP-seq, crosslinking immunoprecipitation-high-throughput sequencing; CSC, cancer stem cell; EMT, epithelial-mesenchymal transition; FPS, first progression survival; GC, gastric cancer; GCSC, gastric cancer stem cell; hnRNPA2B1, heterogeneous nuclear ribonucleoprotein A2B1; IC50, half-maximal inhibitory concentration; IF, immunofluorescence; IgG, immunoglobulin G; IHC, immunohistochemistry; KEGG, Kyoto Encyclopedia of Genes and Genomes; MAPK, mitogen-activated protein kinase; m6A, N6-methyladenosine; MeRIP, methylated RNA-immunoprecipitation; METTL3, methyltransferase 3; mIHC, multispectral immunohistochemistry; NEAT1, nuclear enriched abundant transcript 1; OS, overall survival; PFS, progression free survival; PPS, post progression survival; qPCR, quantitative real-time PCR; RBP, RNA binding proteins; RIP, RNA binding protein immunoprecipitation; SEM, standard error; siRNA, small interfering RNA; TCGA, The Cancer Genome Atlas; TCF7L2, transcription factor 7 like 2; VCR, Vincristine; 5-Fu, 5-fluorouracil. Jiayao Wang, Jiehao Zhang, Hao Liu, and Lingnan Meng contributed equally to this work. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2024 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center. WANG et al. Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an 7100

FAQs

What problem does the study address in gastric cancer?

Chemoresistance is highlighted as a major cause of gastric cancer treatment failure. The study focuses on whether m6A modification and hnRNPA2B1 contribute to this resistance.

How was hnRNPA2B1 expression assessed in the study?

Public datasets were analyzed, and expression was validated experimentally using qPCR, Western blotting, immunofluorescence, and immunohistochemical staining.

What mechanism links hnRNPA2B1 to chemoresistance?

hnRNPA2B1 interacts with and stabilizes the long noncoding RNA NEAT1 in an m6A-dependent manner, and together they enhance GC stemness via the Wnt/β-catenin signaling pathway.

Sep 21, 2026

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