背景:已经报道了细胞质聚(A)结合蛋白-1(PABPC1)在多种癌症类型中的表达。已知该蛋白质调节癌症进展。然而,PABPC1在胰腺癌(PAAD)中表达的影响尚未被研究.这里,我们研究了PABPC1在PAAD中的调控靶点和分子机制。
方法:使用癌症基因组图谱数据库分析,研究PAAD中PABPC1和XII型胶原α1链(COL12A1)的表达及其在肿瘤预后和肿瘤分期中的作用。沉默PABPC1后,进行信使RNA测序和基因本体论(GO)和京都基因和基因组百科全书(KEGG)分析。差异表达基因(DEGs)的表达,细胞活力,凋亡,利用逆转录-定量聚合酶链反应探索细胞迁移和侵袭,细胞计数试剂盒-8测定,流式细胞术测定,和transwell分析,分别。采用Pearson相关分析评价PABPC1与COL12A1表达的关系。在COL12A1过表达后,研究了COL12A1在PABPC1影响的BXPC3细胞行为中的调节功能。
结果:PABPC1和COL12A1在PAAD患者中表达上调,并与不良预后相关。PABPC1沉默后,在BXPC3细胞中观察到474个DEGs。GO和KEGG分析显示前10个DEGs在细胞粘附途径中富集。此外,PABPC1沉默抑制细胞活力,迁移,和侵袭和加速BXPC3细胞凋亡。PABPC1沉默可增加BXPC3细胞中AZGP1和ARHGAP30的表达,并降低CAV1和COL12A1的表达。PABPC1正介导COL12A1表达,而PABPC1敲低诱导BXPC3细胞增殖的抑制,迁移,和入侵。
结论:这项研究的结果表明,PABPC1可能在PAAD中起肿瘤启动子的作用,通过调节COL12A1表达加速BXPC3细胞增殖和转移。
The expression of cytoplasmic poly (A) binding protein-1 (PABPC1) has been reported in multiple cancer types. This protein is known to modulate cancer progression. However, the effects of PABPC1 expression in pancreatic adenocarcinoma (PAAD) have not been investigated. Here, we investigate the regulatory targets and molecular mechanisms of PABPC1 in PAAD.
PABPC1 and collagen type XII α1 chain (COL12A1) expression in PAAD and their role in tumor prognosis and tumor stage were investigated using The Cancer Genome Atlas database analysis. After silencing PABPC1, messenger RNA sequencing and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. The expression of differentially expressed genes (DEGs), cell viability, apoptosis, and cell migration and invasion were explored using reverse transcription-quantitative polymerase chain reaction, Cell Counting Kit-8 assay, flow cytometry assay, and transwell assay, respectively. The relationship between PABPC1 and COL12A1 expression was assessed by Pearson\'s correlation analysis. The regulatory function of COL12A1 in PABPC1-affected BXPC3 cell behavior was studied after COL12A1 was overexpressed.
PABPC1 and COL12A1 expression was upregulated in patients with PAAD and was linked to poor prognosis. Four hundred and seventy-four DEGs were observed in BXPC3 cells after PABPC1 silencing. GO and KEGG analyses revealed that the top 10 DEGs were enriched in cell adhesion pathways. Additionally, PABPC1 silencing inhibited cell viability, migration, and invasion and accelerated apoptosis in BXPC3 cells. PABPC1 silencing increased AZGP1 and ARHGAP30 expression and decreased CAV1 and COL12A1 expression in BXPC3 cells. PABPC1 positively mediated COL12A1 expression, whereas PABPC1 knockdown induced the inhibition of BXPC3 cell proliferation, migration, and invasion.
The results of this study indicate that PABPC1 may function as a tumor promoter in PAAD, accelerating BXPC3 cell proliferation and metastasis by regulating COL12A1 expression.