Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People's Republic of China.
Department of General Surgery, Qilu Hospital (Qingdao) of Shandong University, Qingdao, Shandong, 266035, People's Republic of China.
J Mammary Gland Biol Neoplasia. 2020 Mar;25(1):37-50. doi: 10.1007/s10911-020-09443-6. Epub 2020 Feb 6.
Breast carcinoma(BC)is the most common cancer type among females globally. Understanding the molecular pathways that trigger the development of BC is crucial for both prevention and treatment. As such, the role of transcription factors (TFs) in the development of BC is a focal point in this field. CREB3s play a critical role in initiating the unfolded protein response (UPR); however, the role of CREB3 family members in breast cancer development remains largely unknown. Here, we mined the ONCOMINE database for the transcriptional data of CREB3s in patients with BC. Then, the regulatory functions of a novel TF, CREB3L4, were investigated. CREB3L4 knockdown in MDA-MB-231 and MCF-7 cells suppressed proliferation and promoted apoptosis and cell cycle arrest. ChIP assays confirmed that CREB3L4 can directly bind to the PCNA promoter region, suggesting that the PCNA protein may be functionally downstream of CREB3L4. Additionally, the expression level of CREB3L4 was assessed using our cohort. CREB3L4 is upregulated in breast cancer tissues and is significantly associated with histological grade and tumour size (P = 0.001 and P < 0.001, respectively). Furthermore, PCNA expression was upregulated in breast cancer tissues and positively correlated with CREB3L4. In summary, CREB3L4 may play an important role in the progression of human BC and may serve as a therapeutic target.
乳腺癌（BC）是全球女性中最常见的癌症类型。了解引发 BC 发展的分子途径对于预防和治疗都至关重要。因此，转录因子（TFs）在 BC 发展中的作用是该领域的重点。CREB3s 在启动未折叠蛋白反应（UPR）中起着关键作用；然而，CREB3 家族成员在乳腺癌发展中的作用在很大程度上仍然未知。在这里，我们从 ONCOMINE 数据库中挖掘了 CREB3s 在 BC 患者中的转录数据。然后，研究了一种新型 TF CREB3L4 的调节功能。在 MDA-MB-231 和 MCF-7 细胞中敲低 CREB3L4 可抑制增殖，促进细胞凋亡和细胞周期停滞。ChIP 测定证实 CREB3L4 可以直接结合 PCNA 启动子区域，表明 PCNA 蛋白可能是 CREB3L4 的功能下游。此外，我们还使用队列评估了 CREB3L4 的表达水平。CREB3L4 在乳腺癌组织中上调，与组织学分级和肿瘤大小显著相关（P=0.001 和 P<0.001）。此外，PCNA 在乳腺癌组织中的表达上调，并与 CREB3L4 呈正相关。总之，CREB3L4 可能在人类 BC 的进展中起重要作用，并可能成为治疗靶点。
