Oncogenic messenger RNA transcripts containing microRNA seed-region binding sites (miRNA-targeted oncogenic mRNA)

Oncogenic messenger RNA (mRNA) transcripts containing microRNA (miRNA) seed-region binding sites are a class of therapeutic targets defined by their susceptibility to post-transcriptional regulation by small non-coding RNAs. These transcripts possess specific sequences, typically within their 3' untranslated regions (3' UTRs), that are complementary to the 'seed region' (nucleotides 2-8) of tumor-suppressive microRNAs [Bartel, 2009]. In healthy cells, the binding of these miRNAs to the mRNA targets facilitates gene silencing through translational repression or mRNA degradation via the RNA-induced silencing complex (RISC). In many cancers, the downregulation of these regulatory miRNAs leads to the pathological stabilization and overexpression of oncogenic proteins such as MYC, BCL2, and MET, which drive tumor progression and resistance to therapy [Lin & Gregory, 2015]. Therapeutic interventions, such as miRNA mimics (e.g., MRX34 or MesomiR-1), are designed to restore this natural regulatory mechanism by binding to these seed-region sites to suppress oncogene expression [Rupaimoole & Slack, 2017]. Despite their potential, targeting these transcripts faces challenges including off-target effects due to the multi-target nature of miRNAs and the requirement for efficient, non-toxic delivery systems to reach the tumor site [Hong et al., 2020].

Other names

miRNA-regulated oncogenesMicroRNA-responsive oncogenic transcripts3' UTR seed-match mRNAOncogenic mRNA targets of microRNAs

Agonism of the RNA-induced silencing complex (RISC) to induce sequence-specific cleavage or translational inhibition of target oncogenic mRNA transcripts [Bartel, 2009].