MicroRNA-34a response element-containing oncogene messenger RNAs (miR-34a target mRNAs)

MicroRNA-34a (miR-34a) response element-containing oncogene messenger RNAs (mRNAs) are a diverse group of transcripts that are post-transcriptionally regulated by the tumor-suppressive microRNA, miR-34a (He et al., 2007, Nature). These mRNAs encode critical proteins that drive various hallmarks of cancer, including cell cycle progression (e.g., CDK4, CDK6, E2F3), anti-apoptosis (e.g., BCL2), and oncogenic signaling (e.g., MET, MYC, AXL) (Slabakova et al., 2017, Cancer Letters). miR-34a exerts its regulatory effect by binding to specific seed sequences, known as microRNA response elements (MREs), typically located within the 3' untranslated regions (UTRs) of these target mRNAs. This binding event leads to the degradation of the mRNA transcript or the inhibition of its translation, thereby silencing multiple oncogenic pathways simultaneously. In many human malignancies, miR-34a expression is frequently lost or downregulated, leading to the pathological overexpression of these oncogenic targets and promoting tumor growth and metastasis. Therapeutic strategies, such as the miR-34a mimic MRX34, were developed to restore miR-34a levels and re-establish the repression of this oncogenic network (Beg et al., 2017, Investigational New Drugs). However, clinical development has faced significant challenges, including severe immune-mediated toxicities such as cytokine release syndrome, which led to the termination of early-phase trials.

Other names

miR-34a targetsmiR-34a-regulated oncogenesMicroRNA-34a response elementsMRE-containing mRNAs

RNA interference-mediated gene silencing