A Review and In Silico Analysis of Tissue and Exosomal Circular RNAs: Opportunities and Challenges in Thyroid Cancer

SIMPLE SUMMARY: Thyroid cancer is the most common endocrine neoplasm. Recently, knowledge of the molecular genetic changes of thyroid cancer has dramatically improved. Understanding the roles of these molecular changes in thyroid cancer tumorigenesis and progression is essential in developing a successful treatment strategy and improving disease outcomes. As a family of non-coding RNAs, circular RNAs (circRNAs) have been involved in several aspects of the physiological and pathological processes of the cells. The roles of circRNAs in cancer development and progress are evident. In the current review, we aimed to explore the clinical potential of circRNAs as potential diagnostic, prognostic, and therapeutic targets in thyroid cancer. Furthermore, screening the genome-wide circRNAs and performing functional enrichment analyses for all associated dysregulated circRNAs in thyroid cancer have been done. Given the unique advantages circRNAs have, such as superior stability, higher abundance, and presence in different body fluids, this family of non-coding RNAs could be promising diagnostic and prognostic biomarkers and potential therapeutic targets for thyroid cancer. ABSTRACT: Thyroid cancer (TC) is the most common endocrine tumor. The genetic and epigenetic molecular alterations of TC have become more evident in recent years. However, a deeper understanding of the roles these molecular changes play in TC tumorigenesis and progression is essential in developing a successful treatment strategy and improving patients’ prognoses. Circular RNAs (circRNAs), a family of non-coding RNAs, have been implicated in several aspects of carcinogenesis in multiple cancers, including TC. In the current review, we aimed to explore the clinical potential of circRNAs as putative diagnostic, prognostic, and therapeutic targets in TC. The current analyses, including genome-wide circRNA screening and functional enrichment for all deregulated circRNA expression signatures, show that circRNAs display atypical contributions, such as sponging for microRNAs, regulating transcription and translation processes, and decoying for proteins. Given their exceptional clinical advantages, such as higher stability, wider abundance, and occurrence in several body fluids, circRNAs are promising prognostic and theranostic biomarkers for TC.