Department of Gastroenterology, Anhui University of Science and Technology Affiliated Fengxian Hospital, Shanghai University of Medicine and Health Sciences Affiliated Sixth People's Hospital South Campus, Shanghai Fengxian District Central Hospital, Shanghai 201499, P.R. China.
School of Medicine, Anhui University of Science and Technology, Huainan, Anhui 232001, P.R. China.
Int J Mol Med. 2021 May;47(5). doi: 10.3892/ijmm.2021.4899. Epub 2021 Mar 2.
Recent studies have reported that the expression levels of far upstream element‑binding protein 1 (FUBP1) were upregulated and served a crucial role in several types of cancer. However, the underlying molecular mechanisms and clinical significance of FUBP1 in pancreatic adenocarcinoma (PAAD) remain unclear. The present study aimed to determine the expression levels of FUBP1 in patients with PAAD and subsequently investigated the biological functions and mechanisms of FUBP1 using assays. FUBP1 expression levels and survival outcomes in patients with PAAD were analyzed using The Cancer Genome Atlas and starBase databases. Reverse transcription‑quantitative PCR was used to analyze the mRNA expression levels of FUBP1 in PAAD and adjacent normal tissues. In addition, the expression of FUBP1 was knocked down with small interfering RNA and overexpressed using FUBP1‑overexpressed plasmids, and the effects on biological functions, including cell proliferation, migration and invasion, were investigated. Western blotting and immunofluorescence assays were used to determine the role of FUBP1 in epithelial‑mesenchymal transition (EMT). The results of the present study revealed that the expression levels of FUBP1 were upregulated in PAAD tissues compared with adjacent normal tissues and the upregulated expression was significantly associated with poor survival. The knockdown of FUBP1 expression significantly inhibited the proliferative, migratory and invasive abilities of the PAAD PaTu8988 cell line, while the overexpression of FUBP1 promoted cell proliferation, migration and invasion in the PAAD SW1990 cell line. Furthermore, the knockdown of FUBP1 downregulated the expression levels of EMT‑related markers, including N‑cadherin, β‑catenin and vimentin, while the expression levels of E‑cadherin were upregulated. The knockdown of FUBP1 was also revealed to regulate the TGFβ/Smad signaling cascade by downregulating phosphorylated‑Smad2/3 and TGFβ1 expression levels. Conversely, the overexpression of FUBP1 reversed these effects. In conclusion, the findings of the present study indicated that FUBP1 may be a potential oncogene that mediates the EMT of PAAD via TGFβ/Smad signaling. These data suggested that FUBP1 may represent a potential biomarker for the diagnosis of PAAD or a target for the treatment of patients with PAAD.
最近的研究报告称，远上游元件结合蛋白 1（FUBP1）的表达水平上调，并在几种类型的癌症中发挥关键作用。然而，FUBP1 在胰腺导管腺癌（PAAD）中的潜在分子机制和临床意义仍不清楚。本研究旨在确定 FUBP1 在 PAAD 患者中的表达水平，随后使用 分析研究 FUBP1 的生物学功能和机制。使用癌症基因组图谱和 starBase 数据库分析 PAAD 患者的 FUBP1 表达水平和生存结果。使用逆转录-定量 PCR 分析 PAAD 和相邻正常组织中 FUBP1 的 mRNA 表达水平。此外，使用小干扰 RNA 敲低 FUBP1 的表达，并使用 FUBP1 过表达质粒过表达，研究其对包括细胞增殖、迁移和侵袭在内的生物学功能的影响。Western blot 和免疫荧光分析用于确定 FUBP1 在上皮-间充质转化（EMT）中的作用。本研究结果表明，与相邻正常组织相比，FUBP1 在 PAAD 组织中的表达上调，且上调表达与不良生存显著相关。FUBP1 表达的敲低显著抑制 PAAD PaTu8988 细胞系的增殖、迁移和侵袭能力，而过表达 FUBP1 则促进 PAAD SW1990 细胞系的细胞增殖、迁移和侵袭。此外，FUBP1 的敲低下调了 EMT 相关标志物的表达水平，包括 N-钙黏蛋白、β-连环蛋白和波形蛋白，而上调了 E-钙黏蛋白的表达水平。FUBP1 的敲低还通过下调磷酸化 Smad2/3 和 TGFβ1 的表达水平来调节 TGFβ/Smad 信号级联。相反，FUBP1 的过表达则逆转了这些效应。综上所述，本研究结果表明，FUBP1 可能是一种潜在的癌基因，通过 TGFβ/Smad 信号通路介导 PAAD 的 EMT。这些数据表明，FUBP1 可能是 PAAD 诊断的潜在生物标志物或治疗 PAAD 患者的靶标。
