Circular RNAs: key regulators in cancer stem cell dynamics.

Circular RNAs (circRNAs) are non-coding RNAs with single stranded structure devoid of a 5’ cap and poly-A tail. Although the first circRNA was discovered in the 1970s, the abundance and significance of circRNAs was only realized with the advent of high-throughput RNA-sequencing technologies and bioinformatics analysis. The recent studies have highlighted the variable expression of circRNAs in patient tumor samples. Cancer stem cells (CSCs) are thought to be responsible for initiation and progression of tumors. The cancer stem cell hypothesis states that a small subpopulation of cells within the tumor possesses the ability to self-renew and differentiate into non-stem cells of the tumor. CSCs have the characteristic features of chemo- and radio-resistance, the ability to metastasize, and are often linked with cancer relapse. The clinical data indicates a negative correlation between the proportion of CSCs in tumors and the overall survival of cancer patients. The higher the number of CSCs in a tumor sample, the more aggressive is the tumor. Targeting CSCs is, therefore, a potent therapeutic approach in cancer treatment. This review provides a comprehensive overview of circRNAs and critically evaluates their role in the regulation of CSCs.