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.

中文翻译：

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新型转录因子CREB3L4有助于人类乳腺癌的发展。

乳腺癌（BC）是全球女性中最常见的癌症类型。了解触发BC发生的分子途径对于预防和治疗都至关重要。这样，转录因子（TFs）在BC的发展中的作用是该领域的重点。CREB3在启动未折叠的蛋白质反应（UPR）中起关键作用；然而，CREB3家族成员在乳腺癌发展中的作用仍然未知。在这里，我们从ONCOMINE数据库中挖掘了BC患者CREB3的转录数据。然后，研究了新型TF CREB3L4的调控功能。MDA-MB-231和MCF-7细胞中的CREB3L4抑制可抑制增殖并促进细胞凋亡和细胞周期停滞。ChIP分析证实CREB3L4可以直接结合PCNA启动子区域，提示PCNA蛋白可能在功能上位于CREB3L4的下游。此外，使用我们的队列评估了CREB3L4的表达水平。CREB3L4在乳腺癌组织中上调，并且与组织学分级和肿瘤大小显着相关（P  = 0.001和P  <0.001）。此外，PCNA表达在乳腺癌组织中上调，并与CREB3L4正相关。总之，CREB3L4可能在人类BC的进展中起重要作用，并且可以作为治疗靶标。