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

作者：Jiayao Wang, Jiehao Zhang, Hao Liu, Lingnan Meng, Xianchun Gao, Yihan Zhao, Chen Wang, Xiaoliang Gao, Ahui Fan, Tianyu Cao, Daiming Fan, Xiaodi Zhao, Yuanyuan Lu · 发表于：癌症：英文版 · 年份：2024 · DOI：10.1002/cac2.12534 · 被引用次数：62 · 研究领域：Cancer-related molecular mechanisms research、RNA Research and Splicing、Cancer-related gene regulation

Abstract Background Chemoresistance is a major cause of treatment failure in gastric cancer (GC). Heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) is an N6‐methyladenosine (m 6 A)‐binding protein involved in a variety of cancers. However, whether m 6 A 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 hnRNPA2B1 in GC chemoresistance were investigated both in vitro and in vivo. RNA sequencing, methylated RNA immunoprecipitation, RNA immunoprecipitation, and RNA stability assay were performed to assess the association between hnRNPA2B1 and the binding RNA. The role of hnRNPA2B1 in maintenance of GC stemness was evaluated by bioinformatic analysis, qPCR, Western blotting, immunofluorescence, and sphere formation assays. The expression patterns of hnRNPA2B1 and downstream regulators in GC specimens from patients who received adjuvant chemotherapy were analyzed by RNAscope and multiplex immunohistochemistry. Results Elevated expression of hnRNPA2B1 was found in GC cells and tissues, especially in multidrug‐resistant (MDR) GC cell lines. The expression of hnRNPA2B1 was associated with poor outcomes of GC patients, especial...