College of Life and Health Sciences, Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, Hubei 430000, P.R. China.
Yueyang People's Hospital, Yueyang Hospital Affiliated to Hunan Normal University, Yueyang Breast Disease Diagnosis and Treatment Technology Research Center, Yueyang, Hunan 414000, P.R. China.
Oncol Rep. 2023 Aug;50(2). doi: 10.3892/or.2023.8594. Epub 2023 Jun 30.
Glucosamine‑phosphate N‑acetyltransferase 1 (GNPNAT1) is a member of the acetyltransferase superfamily, related to general control non‑depressible 5 (GCN5). It has been documented that GNPNAT1 expression is increased in lung cancer, whereas its involvement in breast cancer (BC) remains to be further investigated. The present study aimed to evaluate the expression levels of GNPNAT1 in BC and its effect on BC stem cells (BCSCs). The Cancer Genome Atlas (TCGA) database was used for the analysis of the expression of GNPNAT1 and its clinical significance. Cox regression and logistic regression analyses were used to evaluate prognosis‑related factors. The GNPNAT1‑binding protein network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) application. The biological signaling pathways implicated in GNPNAT1 were investigated through function enrichment analysis including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis. The single‑sample GSEA method was used to investigate the connection between the level of immune infiltration and GNPNAT1 expression in BC. GNPNAT1 expression was upregulated in patients with BC and was significantly associated with a poor prognosis. GNPNAT1 and its co‑expressed genes were mostly enriched in nuclear transport, Golgi vesicle transport, ubiquitin‑like protein transferase activity and ribonucleoprotein complex binding, as determined using functional enrichment analysis. GNPNAT1 expression was positively associated with Th2 cells and T‑helper cells, and negatively associated with plasmacytoid dendritic cells, CD8 T‑cells and cytotoxic cells. Additionally, the GNPNAT1 expression levels were considerably increased in BCSCs. GNPNAT1 knockdown markedly decreased the stemness ability of SKBR3 and Hs578T cells, including the production of CSC markers and mammosphere or clone formation, while GNPNAT1 overexpression increased the stemness level. Hence, the findings of the present study demonstrate that GNPNAT1 may be exploited as a novel prognostic biomarker and therapeutic target for BC.
葡萄糖胺-磷酸-N-乙酰转移酶 1（GNPNAT1）是乙酰转移酶超家族的一员，与一般控制不可抑制 5（GCN5）有关。有文献报道 GNPNAT1 在肺癌中的表达增加，但其在乳腺癌（BC）中的作用仍有待进一步研究。本研究旨在评估 GNPNAT1 在 BC 中的表达水平及其对 BC 干细胞（BCSCs）的影响。本研究利用癌症基因组图谱（TCGA）数据库分析 GNPNAT1 的表达及其临床意义。Cox 回归和逻辑回归分析用于评估预后相关因素。使用 Search Tool for the Retrieval of Interacting Genes/Proteins（STRING）应用程序构建 GNPNAT1 结合蛋白网络。通过功能富集分析，包括基因本体论、京都基因与基因组百科全书和基因集富集分析，研究了与 GNPNAT1 相关的生物学信号通路。使用单样本 GSEA 方法研究了 BC 中免疫浸润水平与 GNPNAT1 表达之间的关系。GNPNAT1 在 BC 患者中的表达上调，且与预后不良显著相关。GNPNAT1 及其共表达基因主要富集于核转运、高尔基小泡转运、泛素样蛋白转移酶活性和核糖核蛋白复合物结合，这是通过功能富集分析确定的。GNPNAT1 表达与 Th2 细胞和 T 辅助细胞呈正相关，与浆细胞样树突状细胞、CD8 T 细胞和细胞毒性细胞呈负相关。此外，BCSCs 中 GNPNAT1 的表达水平显著增加。GNPNAT1 敲低显著降低 SKBR3 和 Hs578T 细胞的干性能力，包括产生 CSC 标志物和形成乳腺球体或克隆，而 GNPNAT1 过表达则增加了干性水平。因此，本研究的结果表明，GNPNAT1 可作为 BC 的新型预后生物标志物和治疗靶点。
