Department of Breast Surgical Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
The 2nd Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
Hum Mol Genet. 2023 May 18;32(11):1850-1863. doi: 10.1093/hmg/ddad022.
Breast cancer (bc) is the second most common type of human malignancies with highest morbidity and mortality in the female population. Therefore, it is essential to develop novel and effective therapies for bc treatment. The main aim of the current study is to investigate the functions of CEBPB and THBS2 in bc and the underlying mechanism. Reverse transcription-quantitative real-time polymerase chain reaction and western blot were performed for the measurement of ribonucleic acids and proteins. Function and mechanism assays were, respectively, conducted for the evaluation of bc biological behaviors and exploration of the potential correlation of genes. According to bioinformatics analyses and experimental results, THBS2, up-regulated in bc tissues and cell lines, could facilitate cell migration, invasion and EMT in bc. CEBPB was validated to facilitate miR-29a-3p transcription, thus negatively modulating THBS2 expression. The results of rescue experiments reflected that CEBPB could regulate the malignant behaviors of bc cells via THBS2. Furthermore, CEBPB was ascertained to inhibit the transcription of B3GALTL to affect THBS2 protein O-fucosylation and secretion. The interaction between THBS2 and ITGB1 was confirmed, and THBS2 was found to activate the PI3K/AKT signaling pathway. To conclude, CEBPB could restrain bc cell migration, invasion and EMT via inhibition on THBS2 expression and O-fucosylation.
乳腺癌（bc）是人类恶性肿瘤中第二常见的类型，在女性人群中发病率和死亡率最高。因此，开发新的有效的 bc 治疗方法至关重要。本研究的主要目的是研究 CEBPB 和 THBS2 在 bc 中的功能及其潜在机制。采用逆转录定量实时聚合酶链反应和 Western blot 法检测 RNA 和蛋白质。分别进行功能和机制检测，以评估 bc 的生物学行为，并探讨基因之间的潜在相关性。根据生物信息学分析和实验结果，THBS2 在 bc 组织和细胞系中上调，可促进 bc 中的细胞迁移、侵袭和 EMT。CEBPB 被证实可促进 miR-29a-3p 的转录，从而负调控 THBS2 的表达。挽救实验的结果反映了 CEBPB 可通过 THBS2 调节 bc 细胞的恶性行为。此外，CEBPB 被确定可抑制 B3GALTL 的转录，从而影响 THBS2 蛋白的 O-岩藻糖基化和分泌。证实了 THBS2 与 ITGB1 之间的相互作用，并且发现 THBS2 可激活 PI3K/AKT 信号通路。总之，CEBPB 可通过抑制 THBS2 的表达和 O-岩藻糖基化来抑制 bc 细胞的迁移、侵袭和 EMT。
