Zinc finger E-box-binding homeobox 2 messenger RNA 3' untranslated region (ZEB2 mRNA 3' UTR)

The ZEB2 mRNA 3' UTR is a large, non-coding regulatory segment of the Zinc finger E-box-binding homeobox 2 (ZEB2) transcript, acting as a central hub for post-transcriptional gene regulation [1, 5]. It is characterized by an extensive length (approximately 8.3 kb in humans) and contains numerous conserved binding sites for microRNAs (miRNAs), most notably the miR-200 family [1, 10]. This region facilitates a double-negative feedback loop where miR-200 members suppress ZEB2 expression by binding to the 3' UTR, while ZEB2 protein transcriptionally represses the miR-200 cluster [1, 3]. This regulatory axis is a master switch for the epithelial-mesenchymal transition (EMT), a process critical for embryonic development, wound healing, and cancer metastasis [3, 20]. Dysregulation of the ZEB2 3' UTR, through either miRNA depletion or mutations in binding sites, leads to ZEB2 overexpression, which promotes tumor invasion, chemoresistance, and poor prognosis in various cancers [4, 9]. Conversely, loss-of-function mutations in the ZEB2 gene, including those affecting the 3' UTR's regulatory capacity, are associated with Mowat-Wilson syndrome [5, 14]. Therapeutic approaches targeting this region include the use of miRNA mimics to restore suppression or antisense oligonucleotides (ASOs) to induce mRNA degradation, aiming to inhibit EMT and sensitize tumors to chemotherapy [2, 18, 28].

Other names

SIP1 mRNA 3' UTRSMADIP1 mRNA 3' UTRZFHX1B mRNA 3' UTRZinc finger E-box-binding protein 2 mRNA 3' UTR

miRNA-mediated translational repression and mRNA degradation; Antisense-mediated RNase H1-dependent cleavage