Background: Small nuclear ribonucleoproteins (snRNPs) complexes of protein and noncoding RNA accumulate in the cell nucleus and catalyze pre-mRNA splicing to form the spliceosome. This study aimed to investigate the role of the spliceosome, splicing factor 3b subunit 1 (SF3B1), in AGS and MKN28 human gastric cancer cells in vitro, including gene knockdown with small interfering RNA (siRNA), and the use of the selective mRNA splicing inhibitor of SF3B1, pladienolide B. Material/Methods: In AGS and MKN28 human gastric cancer cells, SF3B1expression was inhibited with siRNA and pladienolide B. Following SF3B1 inhibition, the Cell Counting Kit-8 (CCK-8) assay measured cell proliferation, and flow cytometry was used to investigate cell apoptosis and cell cycle arrest. The downstream HOXA10 and AKT pathways were studied by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. The presence of alternative splicing, or differential splicing, of single-gene coding for multiple proteins, was analyzed using The Cancer Genome Atlas (TCGA) SpliceSeq. Results: Inhibition of SF3B1 reduced the proliferation rate of AGS and MKN28 human gastric cancer cells by inducing apoptosis and G2/M phase arrest. SF3B1 knockdown resulted in reduced homeobox A10 (HOXA10) mRNA expression and expression of long noncoding RNA (lncRNA) isoforms of HOXA10 (exons 1 and 3) and HOXA10 (exons 2 and 3). SF3B1 inhibition increased PTEN levels and reduced AKT protein phosphorylation. Conclusions: In AGS and MKN28 human gastric cancer cells in vitro, inhibition of SF3B1 reduced cell proliferation, induced apoptosis, and resulted in cell cycle arrest by regulating HOXA10 splicing.
The capecitabine and oxaliplatin (CapeOX) regimen is a commonly used adjuvant chemotherapeutic regimen for gastric cancer (GC). However, some patients exhibit a poor chemotherapy response due to genetic differences among individuals. Therefore, finding an effective sensitization strategy for CapeOX is important in the treatment of GC. The present study aimed to investigate the predictive biomarkers of the CapeOX chemotherapeutic outcomes for patients with GC. A total of 30 differentially expressed genes (DEGs) were identified using the gene expression profiles from The Cancer Genome Atlas capecitabine and oxaliplatin treatment GC cases and seven key DEGs [uroplakin-1b (UPK1B), fatty acid-binding protein, heart (FABP3), cystatin-M, caspase-5 (CASP5), corticosteroid 11-β-dehydrogenase isozyme 2, cytochrome P450 4X1 (CYP4X1) and epidermal growth factor receptor kinase substrate 8-like protein 3] were associated with survival. Gene validation was performed in clinical samples divided into recurrence and nonrecurrence groups. Patients with high or low expression of UPK1B, FABP3, CASP5 and CYP4X1 had markedly different overall survival rates. A model was established and the area under the curve of the receiver operating characteristic reached 0.875 (0.793-0.957), indicating that the model had good sensitivity and specificity.
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