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hnRNPA2B1 regulates the alternative splicing of BIRC5 to promote gastric cancer progression

Authors
  • Peng, Wei-zhao1
  • Zhao, Jin1
  • Liu, Xin1
  • Li, Chao-feng1
  • Si, Shuang1
  • Ma, Ren1
  • 1 China-Japan Friendship Hospital, Beijing, 100029, China , Beijing (China)
Type
Published Article
Journal
Cancer Cell International
Publisher
Springer (Biomed Central Ltd.)
Publication Date
May 27, 2021
Volume
21
Issue
1
Identifiers
DOI: 10.1186/s12935-021-01968-y
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundSystematic profiling studies have implicated regulators of pre-mRNA splicing as important disease determinants in gastric cancer (GC), but the underlying mechanisms have remained elusive. Here we focused on hnRNPA2B1 splicing factor-dependent mechanisms governing GC development.MethodsThe expression of hnRNPA2B1 was analyzed among the Cancer Genome Atlas (TCGA) datasets of GC and validated at mRNA level. The function of hnRNPA2B1 in GC cells was analyzed and its downstream gene was identified using RNA immunoprecipitation. Further, effect of hnRNPA2B1 on BIRC5 alternative splicing was investigated.ResultsWe show that overexpression of hnRNPA2B1 in GC is correlated with poor survival, and hnRNPA2B1 is required for maintaining GC malignant phenotype by promoting cell proliferation, inhibiting cell apoptosis and increasing cell metastasis. Mechanistically, hnRNPA2B1 co-expressed with several core spliceosome components and controls alternative splicing of anti-apoptotic factor BIRC5. BIRC5 isoform 202 (BIRC5-202) played the oncogenic function in GC cells, and overexpression of the BIRC5-202 transcript partly rescued the decrease in cisplatin resistance induced by downregulation of hnRNPA2B1.ConclusionsWe demonstrate that hnRNPA2B1 regulates BIRC5 splicing and might act as a therapeutic target of chemo-resistant GC cells.

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