MicroRNA-205 response elements on ERBB3 messenger RNA (miR-205 MREs on ERBB3 mRNA)

The MicroRNA-205 (miR-205) response elements on ERBB3 messenger RNA (mRNA) are specific regulatory sequences located within the 3' untranslated region (UTR) of the ERBB3 gene. These elements function as binding sites for miR-205, a microRNA that typically acts as a tumor suppressor by recruiting the RNA-induced silencing complex (RISC) to inhibit the translation or promote the degradation of the ERBB3 transcript (Iorio et al., 2009). ERBB3, also known as HER3, is a critical member of the epidermal growth factor receptor (EGFR) family and a key activator of the PI3K/Akt survival pathway. Pathological overexpression of ERBB3, often caused by the downregulation of miR-205, is associated with tumor progression and resistance to HER2-targeted therapies like lapatinib and trastuzumab (Zhang et al., 2013). In various malignancies, such as breast cancer and nasopharyngeal carcinoma, restoring the interaction between miR-205 and these response elements can suppress oncogenic signaling (J BUON, 2020). Therapeutic strategies targeting this interaction include the use of miR-205 mimics to restore gene silencing or small molecules like the HDAC inhibitor entinostat, which upregulates miR-205 expression (Zhang et al., 2013). These response elements thus represent a pivotal node for modulating growth factor signaling and overcoming drug resistance in ERBB3-dependent cancers. Monitoring miR-205 and ERBB3 levels serves as a potential biomarker strategy for identifying patients who may benefit from these targeted interventions.

Other names

miR-205 binding sites on ERBB3 3' UTRHER3 mRNA miR-205 response elementsERBB3 3' UTR microRNA response elementsERBB3-miR-205 interaction site

Drugs targeting this site either mimic the endogenous microRNA (miR-205 mimics) or induce its expression (e.g., Entinostat), leading to sequence-specific binding to the ERBB3 3' UTR. This binding recruits the RNA-induced silencing complex (RISC), which mediates translational repression and mRNA degradation of the ERBB3 transcript, thereby downregulating the HER3 protein and inhibiting downstream oncogenic PI3K/Akt signaling. Alternatively, miRNA-masking oligonucleotides can bind directly to these elements to prevent microRNA-mediated silencing of ERBB3.