Polyadenylate-binding protein cytoplasmic 1 mediates alternative splicing events of immune-related genes in gastric cancer cells

Abstract

Polyadenylate-binding protein cytoplasmic 1 (PABPC1) is dysregulated in malignancies, which is considered as a potential therapeutic target for many cancer types. By alternative splicing (AS) for gastric cancer (GC), we described PABPC1-modulated AS events in this study. PABPC1 expression was analyzed in 408 GC tissues from The Cancer Genome Altas (TCGA) database. Human gastric adenocarcinoma (AGS) cells were transfected with PABPC1-specific small interfering RNA (siPABPC1) with siCtrl as a negative control. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was done for the determination of transcripts. To detect the differentially expressed genes (DEGs) and 10 different types of AS events, RNA sequencing (RNA-seq) was performed. DEGs were analyzed for functional categories including gene ontology, and the Kyoto encyclopedia of genes and genomes pathway were analyzed for DEGs. GC displayed an elevated expression of PABPC1. PABPC1 was efficiently knocked down in AGS cells. Here, we excavated 1234 PABPC1-regulated DEGs, among which 502 were down-regulated and 732 were up-regulated compared to the siCtrl group. A total of 94 DEGs were involved in inflammation and immune response. Results from qRT-PCR validated the up-regulation of 10 immune and inflammation-related DEGs in the siPABPC1 group. PABPC1 deficiency causes 1304 AS events differentially occurred in AGS cells. The most common type of AS events regulated by PABPC2 is alternative 5′ splice sites. qRT-PCR confirmed the transcription level of five immune-related genes, in which AS events were detected in the siPABPC1 group. PABPC1 knockdown mediates AS events and thus the transcript level of immune and inflammation-related genes in AGS cells. PABPC1-regulated oncogenic AS events display potential as targets for therapeutic development.

PABPC1 promotes cell proliferation and metastasis in pancreatic adenocarcinoma by regulating COL12A1 expression

“…The biological effects of PABPC1 expression in major translation zone aggregation, which can enter the nucleus under biological stress 30 . Currently, the role of PABPC1 expression is primarily researched in cancer, neurodegenerative diseases, cardiovascular diseases, and spermatogenesis disorders 12,31 . Chorghade et al demonstrated that the specific upregulation of PABPC1 in cardiomyocytes could trigger protein synthesis and physiological myocardial hypertrophy 32 .…”

“… 30 Currently, the role of PABPC1 expression is primarily researched in cancer, neurodegenerative diseases, cardiovascular diseases, and spermatogenesis disorders. 12 , 31 Chorghade et al demonstrated that the specific upregulation of PABPC1 in cardiomyocytes could trigger protein synthesis and physiological myocardial hypertrophy. 32 Additionally, the inhibition of PABPC1 expression has been certified to influence the replication of Listeria monocytogenes , thus better modulating inflammatory response.…”

“…8,9 Evidence from numerous studies has shown that PABPC1 plays a dual role (tumor promoter or antitumor) in tumor initiation and progression and contributes to tumor cell proliferation, apoptosis, and metastasis and tumor recurrence. 10,11 The upregulation of PABPC1 has been observed in gastric cancer, 12 hepatocellular carcinoma (HCC), 13 and esophageal squamous cell carcinoma (ESCC) 14 and has been linked to poor prognosis. PABPC1 is a potential prognostic marker.…”

“…The upregulation of PABPC1 has been observed in gastric cancer, 12 hepatocellular carcinoma (HCC), 13 and esophageal squamous cell carcinoma (ESCC) 14 and has been linked to poor prognosis. PABPC1 is a potential prognostic marker.…”