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

Abstract

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.

Association of Preoperative NANOG-Positive Circulating Tumor Cell Levels With Recurrence of Hepatocellular Carcinoma

“…We used DAKO En-Vision (K5007) for immunohistochemical analysis, and two pathologists from Southwest Hospital independently completed the pathological assessment of each patient's tissue specimen. The final score of the immune response = the percentage of stained area × the intensity of staining, the staining area score method: 75-100% = 4, 50-74% = 3, 25-49% = 2; staining intensity score: high staining = 3, moderate staining =2, weak staining=1, negative=0, the final score range of staining is 0-12 ( 42 ). Follow-up information of patients was collected.…”

“…The 160 research subjects were divided into three groups according to their ages, young people (≤39), middle-aged people (35,41,(43)(44)(45)(46)(47)(48)(49)(50), and old people (≥50). The results of Fisher's exact test showed that there were 14 young people High expression of nanog occurred in 9 persons (64.3%), 17 out of 50 subjects of middle-aged people had high expression of nanog (34%), and 29 out of 96 subjects of elderly had high expression of nanog (30.2 %) The difference between the above three groups is statistically significant (c2=5.941, P=0.047).…”

Computational prediction of CRISPR-impaired non-coding regulatory regions

“…However, protein abundance of CREB3L1, which belongs to the same TF subfamily as CREB3L4, is predictive of the response of triple negative breast cancer to doxorubicin-based therapy [71]. In a recent paper, Pu et al already identified that expression of CREB4L3 is increased in most breast cancer types, and that the downregulation leads to a decreasing proliferation, induces cell cycle arrest and apoptosis [72]. We observed a CREB3L4 binding site in a genomically modified REM associated to CCDC137.…”

Role of chromosome 1q copy number variation in hepatocellular carcinoma

“…CREB3L4 (cyclic amplification responsive element binding protein 3-like 4) is part of the CREB/ATF family of transcriptional factors, and it is primarily expressed in the prostate gland in humans as well as prostate and breast cancer cell lines[ 22 ]. CREB3L4 has been shown (by immunostaining) to have a higher expression level in cancerous prostate cells than in adjacent noncancerous cells[ 22 ] and it has also been shown to contribute to the progression of breast cancer[ 23 ]. INTS3 (integrator complex subunit 3) is part of the Integrator complex which is associated with the C-terminal domain of RNA polymerase II[ 24 ].…”