The Novel Transcription Factor CREB3L4 Contributes to the Progression of Human Breast Carcinoma

Abstract

AbstractBreast 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.