Breast cancer, one of the most frequently diagnosed and aggressive malignancies, is the major cause of cancer‐related death greatly threatening women health. Polypeptide N‐acetylgalactosaminyltransferase 4 (ppGalNAc‐T4), responsible for the initial step of mucin‐type O‐glycosylation, has been reported to be implicated in diverse types of human tumors. However, the biological role of ppGalNAc‐T4 in breast cancer is still undetermined. In this study, we investigate the effects and mechanism of ppGalNAc‐T4 to breast cancer cell proliferation. From analysis of high throughput RNA sequencing datasets of Gene Expression Omnibus and ArrayExpress, a positive correlation between ppGalNAc‐T4 and the recurrence‐free survival was observed in multigroup of human breast cancer datasets. Moreover, transcriptomes analysis using RNA‐sequencing in MCF7 cells revealed that cell cycle‐related genes induced the effects of ppGalNAc‐T4 on breast cancer cell proliferation. Additionally, investigations showed that ppGalNAc‐T4 impaired cell proliferation in MCF‐7 and MDA‐MB‐231 breast cells. Furthermore, our results suggested that the ppGalNAc‐T4 knockout activated Notch signaling pathway and enhanced cell proliferation. Collectively, our data indicated that ppGalNAc‐T4 affected the proliferation of human breast cancer cells, which appears to be a novel target for understanding the underlying molecular mechanism of breast cancer.

中文翻译：

---

ppGalNAc-T4表达降低促进人乳腺癌细胞增殖

乳腺癌是最常诊断和侵袭性的恶性肿瘤之一，是癌症相关死亡的主要原因，极大地威胁着女性的健康。多肽 N-乙酰半乳糖胺基转移酶 4 (ppGalNAc-T4) 负责粘蛋白型 O-糖基化的初始步骤，据报道与多种类型的人类肿瘤有关。然而，ppGalNAc-T4 在乳腺癌中的生物学作用仍未确定。在这项研究中，我们研究了 ppGalNAc-T4 对乳腺癌细胞增殖的影响和机制。通过对 Gene Expression Omnibus 和 ArrayExpress 的高通量 RNA 测序数据集的分析，在多组人类乳腺癌数据集中观察到 ppGalNAc-T4 与无复发生存率之间存在正相关。而且，在 MCF7 细胞中使用 RNA 测序的转录组分析显示，细胞周期相关基因诱导 ppGalNAc-T4 对乳腺癌细胞增殖的影响。此外，研究表明 ppGalNAc-T4 会损害 MCF-7 和 MDA-MB-231 乳腺细胞的细胞增殖。此外，我们的结果表明 ppGalNAc-T4 敲除激活了 Notch 信号通路并增强了细胞增殖。总的来说，我们的数据表明 ppGalNAc-T4 影响人乳腺癌细胞的增殖，这似乎是了解乳腺癌潜在分子机制的新靶点。此外，我们的结果表明 ppGalNAc-T4 敲除激活了 Notch 信号通路并增强了细胞增殖。总的来说，我们的数据表明 ppGalNAc-T4 影响人乳腺癌细胞的增殖，这似乎是了解乳腺癌潜在分子机制的新靶点。此外，我们的结果表明 ppGalNAc-T4 敲除激活了 Notch 信号通路并增强了细胞增殖。总的来说，我们的数据表明 ppGalNAc-T4 影响人乳腺癌细胞的增殖，这似乎是了解乳腺癌潜在分子机制的新靶点。