The biological impacts of CEBPD on urothelial carcinoma development and progression

Abstract

Urothelial carcinoma (UC), which includes urinary bladder urothelial carcinoma (UBUC) and upper tract urothelial carcinoma (UTUC), is one of the most common malignancies worldwide. Accordingly, a comprehensive understanding of the underlying mechanism governing UC development is compulsory. Aberrant CCAAT/enhancer-binding protein delta (CEBPD), a transcription factor, displays an oncogene or tumor suppressor depending on tumor type and microenvironments. However, CEBPD has been reported to possess a clear oncogenic function in UC through multiple regulation pathways. Genomic amplification of CEBPD triggered by MYC-driven genome instability is frequently examined in UC that drives CEBPD overexpression. Upregulated CEBPD transcriptionally suppresses FBXW7 to stabilize MYC protein and further induces hexokinase II (HK2)-related aerobic glycolysis that fuels cell growth. Apart from the MYC-dependent pathway, CEBPD also downregulates the level of hsa-miR-429 to enhance HK2-associated glycolysis and induce angiogenesis driven by vascular endothelial growth factor A (VEGFA). Additionally, aggressive UC is attributed to the tumor metastasis regulated by CEBPD-induced matrix metalloproteinase-2 (MMP2) overexpression. Furthermore, elevated CEBPD induced by cisplatin (CDDP) is identified to have dual functions, namely, CDDP-induced chemotherapy resistance or drive CDDP-induced antitumorigenesis. Given that the role of CEBPD in UC is getting clear but pending a more systemic reappraisal, this review aimed to comprehensively discuss the underlying mechanism of CEBPD in UC tumorigenesis.

Identification of key biomarkers for predicting CAD progression in inflammatory bowel disease via machine‐learning and bioinformatics strategies

“…CCAAT/enhancer binding protein delta (CEBPD) is an intronless gene encoding a protein known as basic leucine zipper (bZIP) transcription factor. 64 According to the current insights, CEBPD serves as a positive modulator in the production of pro-inflammation factors and activation of innate immune responses. 65,66 For instance, Hungness et al 67 found an increase of CEBPB-and CEBPDmediated IL-6 production in the intestinal epithelial cells stimulated with IL-1β.…”

“…CCAAT/enhancer binding protein delta (CEBPD) is an intronless gene encoding a protein known as basic leucine zipper (bZIP) transcription factor 64 . According to the current insights, CEBPD serves as a positive modulator in the production of pro‐inflammation factors and activation of innate immune responses 65,66 .…”

DPEP Inhibits Cancer Cell Glucose Uptake, Glycolysis and Survival by Upregulating Tumor Suppressor TXNIP

“…Several studies indicate that CEBPB and CEBPD promote metabolic reprogramming and affect glycolysis in various cancer cell types [20][21][22][23][24][25]. Recently, Zhang et al [25] showed evidence that CEBPB promotes glycolysis in colon cancer cells by elevating ENO1.…”

“…Such dependence, often designated as the "Warburg effect" has been widely studied and has been identified as a potential, though challenging, target for therapeutic treatment of cancers [17][18][19]. Moreover, several studies have documented positive regulation of glycolysis by Dpep targets CEBPB and CEBPD [20][21][22][23][24][25]. Here, we describe context-dependent suppression of tumor cell glycolysis by Dpep, the mechanisms by which this occurs via suppression of glucose uptake by upregulation of the tumor suppressor TXNIP, and its relevance to promotion of apoptotic death.…”

Occult urothelial carcinoma with mediastinal metastasis: A case report

“…Urothelial carcinoma (UC) is a common tumor found in clinical settings. The majority of UC (90–95%), resides in the bladder and is known as urinary bladder urothelial carcinoma (UBUC) ( 1 ). In 2020, UBUC ranked as the 10th most commonly diagnosed malignancy, with approximately 573,000 new cases and 213,000 deaths around the world ( 2 ).…”