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. 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.

RNA m6A Methylation Regulators Multi-Omics Analysis in Prostate Cancer

“…At the same time, also studies have found that HNRNPA2B1 was the oncogenic gene in esophageal cancer(ESCA), the increased expression of HNRNPA2B1 could predict adverse prognosis of ESCA by affecting tumor-promoting signaling pathways, silencing HNRNPA2B1 could inhibit the proliferation of ESCA cells (Li et al, 2021). Also overexpression of HNRNPA2B1 is correlated with poor survival in gastric cancer (GC), multiple myeloma (MM) and ovarian cancer and HNRNPA2B1 acts as an oncogenic role in their progression (Yang et al, 2020;Jiang et al, 2021;Peng et al, 2021).…”

Single-nucleus RNA sequencing of midbrain blood-brain barrier cells in schizophrenia reveals subtle transcriptional changes with overall preservation of cellular proportions and phenotypes

“…In addition, transcriptomic analysis of brain samples from 559 schizophrenia patients revealed that changes in the expression of transcript splice variants captured the largest schizophrenia effect [ 109 ]. In our data, endothelial nuclei derived from schizophrenia exhibited reduced expression of HNRNPA2B1 , a gene coding for a heterogeneous ribonucleoprotein involved in the alternative splicing of several genes [ 110 – 112 ] (S. Fig. 2D ).…”

Single-nucleus RNA sequencing of the midbrain blood-brain barrier cells in schizophrenia reveals subtle transcriptional changes with overall preservation of cellular proportions and phenotypes

“…In addition, transcriptomic analysis of brain samples from 559 schizophrenia patients revealed that changes in the expression of transcript splice variants captured the largest schizophrenia effect [6]. In our data, endothelial nuclei derived from schizophrenia depicted reduced expression of HNRNPA2B1, a gene coding for a heterogeneous ribonucleoprotein involved in the alternative splicing of several genes [111][112][113] (S. Figure 2D). However, as the 10X snRNAseq methodology does not allow for the detection of alternative spliced transcripts, our data do not contain alternative splicing information; thus, we cannot evaluate whether the reduced expression of HNRNPA2B1 in schizophrenia affects the transcriptome of endothelial nuclei at the isoform-level.…”