The multifaceted roles of circular RNAs in cancer hallmarks: From mechanisms to clinical implications

Circular RNAs (circRNAs) represent a distinct class of covalently closed RNA species lacking conventional 5' to 3' polarity. Derived predominantly from pre-mRNA transcripts of protein-coding genes, circRNAs arise through back-splicing events of exon-exon or exon-intron junctions. They exhibit tissue- and cell-specific expression patterns and play crucial roles in regulating fundamental cellular processes such as cell cycle dynamics, proliferation, apoptosis, and differentiation. CircRNAs modulate gene expression through a plethora of mechanisms at epigenetic, transcriptional, and post-transcriptional levels, and some can even undergo translation into functional proteins. Recently, aberrant expression of circRNAs has emerged as a significant molecular aberration within the intricate regulatory networks governing hallmarks of cancer. The tumor-specific expression patterns and remarkable stability of circRNAs have profound implications for cancer diagnosis, prognosis, and therapy. This review comprehensively explores the multifaceted roles of circRNAs across cancer hallmarks in various tumor types, underscoring their growing significance in cancer diagnosis and therapeutic interventions. It also details strategies for leveraging circRNA-based therapies and discusses the challenges in using circRNAs for cancer management, emphasizing the need for further research to overcome these obstacles.