PABPC1 通过调节 COL12A1 的表达促进胰腺腺癌的增殖和转移。

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

背景：细胞质多聚（A）结合蛋白-1（PABPC1）的表达已在多种癌症类型中报道。该蛋白已知可调节癌症进展。然而，PABPC1 在胰腺腺癌（PAAD）中的表达的影响尚未被研究。在这里，我们研究了 PABPC1 在 PAAD 中的调节靶标和分子机制。

方法：使用癌症基因组图谱数据库分析，研究了 PAAD 中 PABPC1 和胶原 XII α1 链（COL12A1）的表达及其对肿瘤预后和肿瘤分期的作用。在沉默 PABPC1 后，进行信使 RNA 测序和基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析。使用逆转录定量聚合酶链反应、细胞计数试剂盒-8 测定法、流式细胞术测定法和 Transwell 测定法分别探索差异表达基因（DEGs）的表达、细胞活力、细胞凋亡以及细胞迁移和侵袭。通过 Pearson 相关分析评估 PABPC1 和 COL12A1 表达之间的关系。在用 COL12A1 过表达研究 COL12A1 在 PABPC1 影响的 BXPC3 细胞行为中的调节功能。

结果：PABPC1 和 COL12A1 的表达在 PAAD 患者中上调，并与预后不良相关。在 PABPC1 沉默后，BXPC3 细胞中观察到 474 个差异表达基因。GO 和 KEGG 分析表明，前 10 个 DEGs 富集在细胞黏附途径中。此外，PABPC1 沉默抑制 BXPC3 细胞活力、迁移和侵袭，并加速细胞凋亡。PABPC1 沉默增加了 BXPC3 细胞中 AZGP1 和 ARHGAP30 的表达，降低了 CAV1 和 COL12A1 的表达。PABPC1 正向介导 COL12A1 的表达，而 PABPC1 敲低诱导 BXPC3 细胞增殖、迁移和侵袭的抑制。

结论：本研究结果表明，PABPC1 可能在 PAAD 中作为肿瘤促进因子发挥作用，通过调节 COL12A1 的表达，加速 BXPC3 细胞的增殖和转移。