hnRNPA2B1 regulates the alternative splicing of BIRC5 to promote gastric cancer progression
Abstract Background Systematic 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....
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doaj-27907cf4665a40be9e80af3b86852da12021-05-30T11:23:48ZengBMCCancer Cell International1475-28672021-05-0121111410.1186/s12935-021-01968-yhnRNPA2B1 regulates the alternative splicing of BIRC5 to promote gastric cancer progressionWei-zhao Peng0Jin Zhao1Xin Liu2Chao-feng Li3Shuang Si4Ren Ma5Department of General Surgery, China-Japan Friendship HospitalDepartment of General Surgery, China-Japan Friendship HospitalDepartment of General Surgery, China-Japan Friendship HospitalDepartment of General Surgery, China-Japan Friendship HospitalDepartment of General Surgery, China-Japan Friendship HospitalDepartment of General Surgery, China-Japan Friendship HospitalAbstract Background Systematic 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. Methods The 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. Results We 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. Conclusions We demonstrate that hnRNPA2B1 regulates BIRC5 splicing and might act as a therapeutic target of chemo-resistant GC cells.https://doi.org/10.1186/s12935-021-01968-yhnRNPA2B1BIRC5SplicingGastric cancer |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wei-zhao Peng Jin Zhao Xin Liu Chao-feng Li Shuang Si Ren Ma |
spellingShingle |
Wei-zhao Peng Jin Zhao Xin Liu Chao-feng Li Shuang Si Ren Ma hnRNPA2B1 regulates the alternative splicing of BIRC5 to promote gastric cancer progression Cancer Cell International hnRNPA2B1 BIRC5 Splicing Gastric cancer |
author_facet |
Wei-zhao Peng Jin Zhao Xin Liu Chao-feng Li Shuang Si Ren Ma |
author_sort |
Wei-zhao Peng |
title |
hnRNPA2B1 regulates the alternative splicing of BIRC5 to promote gastric cancer progression |
title_short |
hnRNPA2B1 regulates the alternative splicing of BIRC5 to promote gastric cancer progression |
title_full |
hnRNPA2B1 regulates the alternative splicing of BIRC5 to promote gastric cancer progression |
title_fullStr |
hnRNPA2B1 regulates the alternative splicing of BIRC5 to promote gastric cancer progression |
title_full_unstemmed |
hnRNPA2B1 regulates the alternative splicing of BIRC5 to promote gastric cancer progression |
title_sort |
hnrnpa2b1 regulates the alternative splicing of birc5 to promote gastric cancer progression |
publisher |
BMC |
series |
Cancer Cell International |
issn |
1475-2867 |
publishDate |
2021-05-01 |
description |
Abstract Background Systematic 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. Methods The 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. Results We 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. Conclusions We demonstrate that hnRNPA2B1 regulates BIRC5 splicing and might act as a therapeutic target of chemo-resistant GC cells. |
topic |
hnRNPA2B1 BIRC5 Splicing Gastric cancer |
url |
https://doi.org/10.1186/s12935-021-01968-y |
work_keys_str_mv |
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