Role of circular RNAs in colorectal tumor microenvironment

Circular RNAs (circRNAs) are a class of endogenous noncoding RNA, which were previously considered as a byproduct of RNA splicing error. Numerous studies have demonstrated the altered expression of circRNAs in organ tissues during pathological conditions and their involvements in disease pathogenesis and progression, including cancers. In colorectal cancer (CRC), multiple circRNAs have been identified and characterized as “oncogenic”, given their involvements in the downregulation of tumor suppressor genes and induction of tumor initiation, progression, invasion, and metastasis. Additionally, other circRNAs have been identified in CRC and characterized as “tumor suppressive” based on their ability of inhibiting the expression of oncogenic genes and suppressing tumor growth and proliferation. circRNAs could serve as potential diagnostic and prognostic biomarkers, and therapeutic targets or vectors to be utilized in cancer therapies. This review briefly describes the dynamic changes of the tumor microenvironment inducing immunosuppression and tumorigenesis, and outlines the biogenesis and characteristics of circRNAs and recent findings indicating their roles and functions in the CRC tumor microenvironment. It also discusses strategies and technologies, which could be employed in the future to overcome current cancer therapy challenges associated with circRNAs. [Display omitted] •Oncogenic and tumor suppressive role of circRNA has been proved in distinct CRC setting.•How circRNAs regulates EMT, immune response and angiogenesis in the TME is yet to discover.•Role of exosomal and translatable circRNA in the CRC TME should be studied.•Targeting oncogenic circRNAs and enhancing tumor suppressive circRNAs are potential therapeutic strategies.•CircRNA can be used as diagnostic and prognostic biomarkers in CRC.