The potential of using blood circular RNA as liquid biopsy biomarker for human diseases
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Protein & Cell
REVIEW The potential of using blood circular RNA as liquid biopsy biomarker for human diseases Guoxia Wen1
, Tong Zhou2&
, Wanjun Gu
1&
State Key Laboratory of Bioelectronics, School of Biological Sciences and Medical Engineering, Southeast University, Nanjing 210096, China 2 Department of Physiology and Cell Biology, Reno School of Medicine, University of Nevada, Reno, NV 89557, USA & Correspondence: [email protected] (T. Zhou), [email protected] (W. Gu) Received September 21, 2020 Accepted October 9, 2020
ABSTRACT Circular RNA (circRNA) is a novel class of singlestranded RNAs with a closed loop structure. The majority of circRNAs are formed by a back-splicing process in pre-mRNA splicing. Their expression is dynamically regulated and shows spatiotemporal patterns among cell types, tissues and developmental stages. CircRNAs have important biological functions in many physiological processes, and their aberrant expression is implicated in many human diseases. Due to their high stability, circRNAs are becoming promising biomarkers in many human diseases, such as cardiovascular diseases, autoimmune diseases and human cancers. In this review, we focus on the translational potential of using human blood circRNAs as liquid biopsy biomarkers for human diseases. We highlight their abundant expression, essential biological functions and significant correlations to human diseases in various components of peripheral blood, including whole blood, blood cells and extracellular vesicles. In addition, we summarize the current knowledge of blood circRNA biomarkers for disease diagnosis or prognosis.
KEYWORDS peripheral blood circular RNA, liquid biopsy, human diseases, translational biomarkers INTRODUCTION Liquid biopsy is a biopsy that uses body liquids as the sample source to diagnose, predict the outcome of or monitor the development of human diseases (Rubis et al., 2019; Luo et al., 2020a). Compared to traditional tissue biopsy, liquid biopsy has the advantages of being noninvasive, performed in real-time and accurate (Rubis et al., 2019; Luo
© The Author(s) 2020
et al., 2020a). It has been proven to be applicable to the management of many human diseases, including cancers (Heitzer et al., 2019; Mattox et al., 2019; Rubis et al., 2019), prenatal genetic disorders (Zhang et al., 2019a), heart diseases (Zemmour et al., 2018), schizophrenia (Chen et al., 2020b), transplant rejection (Bloom et al., 2017) and infectious diseases (Burnham et al., 2018; Hong et al., 2018; Blauwkamp et al., 2019; Han et al., 2020a). To date, most liquid biopsy studies have focused on its clinical application in human cancers (reviewed in Siravegna et al., 2017; Heitzer et al., 2019; Mattox et al., 2019; Rubis et al., 2019). For example, a cell-free DNA (cfDNA)-based liquid biopsy test that determines the mutational status of the epidermal growth factor receptor (EGFR) gene was used to guide the response of EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC) patients, which was approved by the FDA in clinical
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