• Circular RNAs in tumorigenesis and cancer diagnosis
  • Zahra-sadat Mousavi,1,* Amir Atashi,2 Roqaye Karimi,3
    1. Student Research Committee, School of Allied Medical Sciences, Shahroud University of Medical Sciences, Shahroud, Iran
    2. Stem Cell and Tissue Engineering Research Center, Shahroud University of Medical Sciences, Shahroud, Iran
    3. Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran


  • Introduction: Cancer is a complex and common disease that has internal and external risks. The incidence and mortality rate of this disease is increasing every year and causes serious problems in world health and public health. For almost two decades, researchers have explored the role of non-coding RNA (ncRNA) in cancer biology. ncRNAs are stable in biological fluids and show tissue-specific expression. ncRNAs can act as biomarkers or key regulators of the cancer gene network. CircRNAs were first identified in viroids by Sanger et al. in 1976 and subsequently found in eukaryotes in 1979 by electron microscopy.
  • Methods: Circular RNAs (circRNAs) are non-coding RNAs that form a circular structure by covalent bonding and are resistant to exonuclease degradation due to the lack of 5′ cap and polyadenylated tails at the 3′ end. They are more stable than linear RNAs and have a longer half-life. CircRNAs are classified into three categories: intronic circRNAs (ciRNAs), exonic circRNAs (ecircRNAs), or exonic-intronic circRNAs (EIciRNAs).
  • Results: CircRNAs have several mechanisms of action: they can act as sponge miRNAs and prevent miRNA binding to mRNA and prevent mRNA degradation. They can act as protein sponges and prevent protein binding to mRNA. CircRNAs may act as local mediators for the transport of specific proteins from the cytoplasm to the nucleus and can also act as structural mediators, accumulating enzymes and substrates and influencing reaction kinetics. CircRNAs can act as transcriptional regulators to control host gene expression. Recent studies have shown that some circRNAs that contain the IRES or N6-methyladenosine (m6A) sequence can be translated into proteins. For example, circFBXW7 contains IRES sequences that can be translated into proteins. CircRNAs can be considered as new biomarkers due to their different expression in tissues and are associated with carcinogenesis and tumor progression by regulating cellular activity.
  • Conclusion: CircRNA has different mechanisms in human cancers, for example circAGFG1 increases expression in Triple-negative Breast Cancer (TNBC), acts as a sponge microRNA for miR-195-5p, and causes TNBC cells to proliferate as well as tumor metastasis in vivo. CircDNMT1 increases expression in Breast Cancer (BRCA) and binds to P53 and AUF1 proteins, and the main mechanism of this circRNA is to increase Dnmt1 translation. CircSHPRH decreases in glioblastoma multiforme (GBM) and produces SHPRH, which suppresses tumors in human glioblastoma. A circRNA can play opposite roles in different cancers by acting as a sponge miRNA on several different mRNAs. For example, circHIPK3 targets miR-7 to enhance colon cancer growth and metastasis, It also targets miR-558 to suppress heparanase expression, which breaks down heparan sulfate chains in the extracellular matrix. Recently, the promising role of exosomal RNAs in cancer diagnosis have discovered. For example, circulating exosomal mRNAs were used to diagnose prostate cancer, and due to the different expression patterns between exosomal mRNAs and tissue mRNAs, urine circulating exosomal mRNAs are used as non-invasive biomarkers for prostate cancer diagnosis.
  • Keywords: CircRNA, Cancer, Tumorigenesis, Diagnosis, miRNA