Ras responsive element binding protein 1 (RREB1) (RREB1)

Ras responsive element binding protein 1 (RREB1) is a large zinc finger transcription factor that plays a pivotal role in the Ras/Raf/MEK/ERK signaling pathway [1, 3]. It specifically binds to Ras-responsive elements (RREs) within the promoters of target genes to either activate or repress their transcription [1, 4]. RREB1 is a key mediator of epithelial-to-mesenchymal transition (EMT) and is frequently overexpressed in various malignancies, including pancreatic, colorectal, and prostate cancers, where it promotes tumor progression and metastasis [1, 2, 5]. In addition to its oncogenic roles, RREB1 is involved in metabolic regulation, particularly in the control of insulin gene expression and glucose homeostasis, with genetic variants linked to type 2 diabetes risk [1, 12]. As a therapeutic target, RREB1 mRNA is being explored for silencing via RNA interference (RNAi) and antisense oligonucleotides (ASOs) to disrupt the feed-forward loops that drive KRAS-mutant cancers [1, 8, 12]. These approaches aim to reduce the expression of RREB1 to restore the levels of tumor-suppressive microRNAs like miR-143 and miR-145 [1, 12]. While still in the preclinical stage, targeting RREB1 mRNA represents a promising strategy for treating undruggable Ras-driven tumors and potentially managing metabolic disorders [1, 15].

Other names

HNTFINBLZ321Zep-1Ras-responsive element-binding protein 1Hindsight homologRREB1 mRNA

RNA interference and antisense-mediated mRNA degradation leading to reduced protein expression and restoration of tumor-suppressive pathways