Circular RNAs (circRNAs) in cancer metastasis: Molecular interactions and possible therapeutic targets

Metastasis is defined as a complicated process in which tumor cells migrate from their primary site to a secondary site for establishing new colonies and ensuring their progression. During this process, cancer cells invade surrounding tissue and enter into bloodstream, which is known as intravasation, and then on reaching to an appropriate site, they exit blood vessels, which is called extravasation. Up to 90% of cancer-related mortality is due to metastasis, and it can reduce the survival rate of patients. Although genetic alterations play a significant role in metastasis of tumor cells, epigenetic changes have been shown to be involved in the process of cancer metastasis. Circular RNAs (circRNAs) are RNA transcripts with no capacity in encoding proteins that exert regulatory effects in cells during physiological functions and their dysregulation is observed in diseases such as diabetes mellitus, neurological diseases, and cancers. cir-cRNAs regulate epithelial-mesenchymal transition (EMT), matrix metalloproteinases (MMPs), and angiogenesis in regulating the invasion of cancer cells. Knock-down of oncogenic circRNAs is important in impairing metastasis in tumors. circRNA-miRNA axis plays a remarkable role in the invasion of tumor cells. Targeting circRNAs regulating tumor invasion is beneficial in impairing cancer malignancy and improving the prognosis and survival rate of patients.