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Diabetic retinopathy (DR), the most frequent complication of diabetes mellitus, is the principal cause of acquired blindness worldwide. Although the roles of circRNAs have been extensively explored, the detailed physiological and pathological functions of circRNAs in DR are less understood. Here, we studied the biological effects of circ-ITCH in diabetic retinal pigment epithelial cells (RPEs) and explored the underlying mechanisms. As our results shown, the RNA expression of circ-ITCH was significantly lower in RPEs isolated from diabetic rats than they were in those isolated from normal rats. While diabetes induced an increase in MMP-2, MMP-9 and TNF-α in RPEs, circ-ITCH overexpression exerted an inhibitory on these increases and knockdown of circ-ITCH reversed the inhibitory. In addition, increased expression of miR-22 in RPEs correlated with diabetes and downregulation of circ-ITCH. Remarkably, in the presence of miR-22 mimics, the effects of circ-ITCH on the MMP-2 and MMP-9 were both antagonized. Collectively, our data supports a cellular signaling cascade in which circ-ITCH-inhibited miR-22 activity modulates the expression of MMP-2, MMP-9 and TNF-α in DR., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Circular RNAs (circRNAs) are a new type of endogenous noncoding RNAs with closed circular structure. Emerging evidence indicates that circRNAs play crucial roles in many biological processes by regulating linear RNA transcription, downstream gene expression and protein production. Meanwhile, recent studies have suggested that circRNAs have the potential to be oncogenic or anti-oncogenic and play vital regulatory roles in the initiation and progression of tumors. Circular RNA itchy E3 ubiquitin protein ligase (circ-ITCH), a novel circular RNA originated from several exons of ITCH and located on chromosome 20q11.22, was proved to be declined in many malignant tumors, such as melanoma and ovarian cancer, resulting in tumor occurrence and progression. This review summarizes the biogenesis, characteristics, and functions of circRNAs, as well as recent progression regarding the biological functions and potential molecular mechanisms of circ-ITCH, and future challenges in cancer research., Competing Interests: Declaration of competing interest The authors have declared that no competing interest exists., (Copyright © 2019 Elsevier Inc. All rights reserved.)

While recent evidence has uncovered that circular RNAs (circRNAs) are vital regulators of carcinogenesis, their role in papillary thyroid cancer (PTC) is not clearly understood. In this study, we reveal that lower levels of circRNA circ-ITCH are expressed in PTC tissues than in normal adjacent tissues. Gain-of-functional assays show that circ-ITCH overexpression suppresses PTC cell proliferation and invasion and promotes apoptosis in vitro. Overexpression of circ-ITCH also leads to impaired tumor growth in vivo. Bioinformatics analysis and luciferase reporter assays demonstrate that circ-ITCH sponges miR-22-3p to upregulate the expression of CBL, an E3 ligase of nuclear β-catenin. Elevated levels of CBL suppress activation of the Wnt/β-catenin pathway and consequently attenuates PTC progression. In summary, our study reveals a novel signaling pathway of circ-ITCH/miR-22-3p/CBL/β-catenin involved in PTC development and progression., (Copyright © 2018 Elsevier Inc. All rights reserved.)