Tumor Cells-derived exosomal CircRNAs: Novel cancer drivers, molecular mechanisms, and clinical opportunities

Recently, circular RNAs (circRNAs) have appealed to a growing interest due to their abundant expression and
potential functions in cancer development. The most biological function of circRNAs may include acting as a
sponge for miRNAs and proteins in different physio/pathological conditions. CircRNAs promote cancer progression
by regulating several procedures such as growth, invasion, metastasis, angiogenesis, and drug resistance.
Emerging evidence has shown that circRNAs frequently have tumor-specific expression, proposing these
molecules serve as diagnostic and prognostic cancer biomarkers. Furthermore, circRNAs may be used as a potential
target for the treatment of cancers as they can sponge oncogenic miRNAs and proteins. Exosomes, a
subtype of extracellular vesicles mediate intercellular communication, contain circRNAs and deliver them to
target cells inducing cancer development through different signaling pathways. Exosomal circRNAs may serve as
a diagnostic and prognostic biomarker for cancers. Targeting exosomes may represent novel approaches for the
treatment of cancers through using them as cell-free therapy and drug-delivery system and inhibiting their
biogenesis and distribution. However, research on circRNAs biology is advancing and some concerns such as
technical issues in the characterization and analysis of circRNAs along with biological understanding gaps
necessary to be considered to transfer this undeveloped field to the vanguard of clinical studies. In this review,
we discuss the existing information on the formation of circRNA and its roles in the tumor as a biomarker and
treatment target. Furthermore, we describe tumor-derived exosomes enclosed circRNAs and their possible roles
in cancer development and their potential as biomarkers and therapeutic approaches.