RBCK1 regulates the progression of ER-positive breast cancer through the HIF1α signaling

Abstract

Breast cancer is the most common malignancy in women on a global scale. It can generally be divided into four main categories, of which estrogen receptor ER-positive breast cancer accounts for most breast cancer cases. RBCK1 protein is an E3 ubiquitin ligase containing the UBL, NZF, and RBR domains. It is well known to exhibit abnormal expression in breast tumors, making it a valuable diagnostic marker and drug target. Additionally, studies have confirmed that in breast cancer, about 25 to 40% of tumors appear as visible hypoxic regions, while in hypoxia, tumor cells can activate the hypoxia-inducing factor HIF1 pathway and widely activate the expression of downstream genes. Previous studies have confirmed that in the hypoxic environment of tumors, HIF1α promotes the remodeling of extracellular matrix, induces the recruitment of tumor-associated macrophages (TAM) and immunosuppression of allogeneic tumors, thereby influencing tumor recurrence and metastasis. This research aims to identify RBCK1 as an important regulator of HIF1α signaling pathway. Targeted therapy with RBCK1 could be a promising treatment strategy for ER-positive breast cancer.

Differential DNA methylation in the brain as potential mediator of the association between traffic‐related PM2.5 and neuropathology markers of Alzheimer's disease

“…RBCK1 , the gene which cg10495669 is assigned to, is involved in carcinogenesis and inflammation pathways. The overexpression of RBCK1 was observed in multiple cancer cells, including renal, colorectal, and breast cells, in in‐vitro experiments 60–62 . The knockdown of RBCK1 in renal cancer cells may induce p53 expressions, and thus, Yu et al.…”

“…in-vitro experiments [60][61][62]. The knockdown of RBCK1 in renal cancer cells may induce p53 expressions, and thus, Yu et al proposed a model in which RBCK1 promoted the ubiquitination and degradation of p53, a protein playing a major role in DNA damage response 62.…”

A novel likely pathogenic homozygous RBCK1 variant in dilated cardiomyopathy with muscle weakness

“…29 And also, its deficiency is a rare inflammatory disorder characterized by amylopectin accumulation in skeletal muscle, causing myopathy and cardiomyopathy, and it is a valuable diagnostic indicator and therapeutic target. 8,30 The investigation of disease-causing mutations has involved the examination of protein expression levels and truncation levels. The abstracts presented do not include the specific investigation of protein expression levels or protein truncation levels and their correlation with the phenotype in the context of DCM resulting from RBCK1 mutation.…”

“…The effect of truncated RBCK1 protein in DCM is manifested by polyglucosan formation in skeletal muscle and myocardium, leading to the progressive onset of muscle weakness and myocardial infarction 29 . And also, its deficiency is a rare inflammatory disorder characterized by amylopectin accumulation in skeletal muscle, causing myopathy and cardiomyopathy, and it is a valuable diagnostic indicator and therapeutic target 8,30 …”

Mechanism of morusin on breast cancer via network pharmacology and in vitro experiments

“…[40][41][42][43] Stable HIF-1 expression encourages glycolysis, invasion transfer, and the emergence of resistance by activating the HIF-1 signal pathway. [44][45][46][47] This implies that alternative targets and pathways may also be activated by morusin. Therefore, further exploration of the role and mechanism of morusin may yield more surprising findings.…”