Academic Journal
N6‐methyladenosine reader hnRNPA2B1 recognizes and stabilizes NEAT1 to confer chemoresistance in gastric cancer
| العنوان: | N6‐methyladenosine reader hnRNPA2B1 recognizes and stabilizes NEAT1 to confer chemoresistance in gastric cancer |
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| المؤلفون: | Wang, Jiayao, Zhang, Jiehao, Liu, Hao, Meng, Lingnan, Gao, Xianchun, Zhao, Yihan, Wang, Chen, Gao, Xiaoliang, Fan, Ahui, Cao, Tianyu, Fan, Daiming, Zhao, Xiaodi, Lu, Yuanyuan |
| المساهمون: | National Natural Science Foundation of China |
| المصدر: | Cancer Communications ; volume 44, issue 4, page 469-490 ; ISSN 2523-3548 2523-3548 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2024 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | 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, especially in those who received 5‐fluorouracil treatment. Silencing hnRNPA2B1 effectively sensitized GC cells to chemotherapy by inhibiting cell proliferation and inducing apoptosis both in vitro and in vivo. Mechanically, hnRNPA2B1 interacted with and stabilized long noncoding RNA NEAT1 in an m 6 A‐dependent manner. Furthermore, hnRNPA2B1 and NEAT1 worked together to enhance the stemness properties of GC cells via Wnt/β‐catenin signaling pathway. In clinical specimens from GC patients subjected to chemotherapy, the expression levels of hnRNPA2B1, ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1002/cac2.12534 |
| الاتاحة: | http://dx.doi.org/10.1002/cac2.12534 https://onlinelibrary.wiley.com/doi/pdf/10.1002/cac2.12534 |
| Rights: | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| رقم الانضمام: | edsbas.5359959C |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/cac2.12534 |
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