Circular RNAs (circRNAs) are a class of RNA molecules with closed loops and high stability. CircRNAs are abundantly expressed in eukaryotic organisms and exhibit both location- and step-specificity. In recent years, circRNAs are attracting considerable research attention attributed to their possible contributions to gene regulation through a variety of actions, including sponging microRNAs, interacting with RNA-binding proteins, regulating transcription and splicing, and protein translation. Growing evidence has revealed that circRNAs play critical roles in the development and progression of diseases, especially in cancers. Without doubt, expanding our understanding of circRNAs will enrich knowledge of cancer and provide new opportunities for cancer therapy. In this review, we provide an overview of the characteristics, functions and functional mechanisms of circRNAs. In particular, we summarize current knowledge regarding the functions of circRNAs in the hallmarks, stemness, resistance of cancer, as well as the possibility of circRNAs as biomarkers in cancer.

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Circular RNAs in Cancer: emerging functions in hallmarks, stemness, resistance and roles as potential biomarkers

A novel circular RNA, circFAT1(e2), inhibits gastric cancer progression by targeting miR-548g in the cytoplasm and interacting with YBX1 in the nucleus.

CircRNAs in lung cancer - Biogenesis, function and clinical implication.

CircRNA_100290 promotes colorectal cancer progression through miR-516b-induced downregulation of FZD4 expression and Wnt/β-catenin signaling.

Circular RNAs were recently identified as a novel type of noncoding RNAs. An increasing number of reports have demonstrated their essential regulatory roles in various biological processes and human diseases, including cancer. However, the role of circRNA in cervical cancer (CC) remains largely unknown. In the current study, we investigated the physiological functions of circ_0067934 during CC development and progression. We found that circ_0067934 was overexpressed in CC tissues and cell lines. Circ_0067934 upregulation was associated with advanced stage, lymph node metastasis, and poor prognosis in CC patients. Knockdown of circ_0067934 suppressed the proliferation, colony formation, migration, invasion, and epithelial-mesenchymal transition of CC cells in vitro. Circ_0067934 loss also inhibited CC tumor growth in vivo. Mechanistically, silencing circ_0067934 increased miR-545 expression. MiR-545 repressed EIF3C expression through targeting its 3'-untranslated region. MiR-545 suppressed the proliferation, migration, and invasion of CC cells, whereas restoration of EIF3C could rescue the effects of circ_0067934 knockdown. Taken together, our findings revealed that circ_0067934 promotes CC progression via miR-545/EIF3C axis. Our study may provide a new insight into the pathogenesis of CC.

Overexpressed circ_0067934 acts as an oncogene to facilitate cervical cancer progression via the miR-545/EIF3C axis.

Objective Circular RNAs are a subgroup of non-coding RNAs and generated by a mammalian genome. The purpose of this study was to investigate the clinical significance, biological function and molecular mechanism of circ_0067934 in human non-small cell lung cancer (NSCLC). Patients and methods We assayed expression level of circ_0067934 in NSCLC tissues and cell lines by Real-time PCR. The associations of circ_0067934 expression with clinicopathologic features and overall survival of patients with NSCLC were statistically analyzed. Biological functions of circ_0067934 were analyzed using MTT and transwell migration and invasion assays in vitro. The expression of EMT-related mRNAs and proteins was assayed using Real-time PCR and Western blot. Results We found that circ_0067934 expression was significantly increased in NSCLC tissues and cell lines. High circ_0067934 expression was significantly associated with TNM stage (p=0.003), lymph node status (p=0.000), and distant metastasis (p=0.017). Moreover, Kaplan-Meier curves showed that higher expression of circ_0067934 led to a significantly poorer survival. Multivariate Cox proportional hazards analysis suggested that circ_0067934 was an independent poor prognostic factor for patients with NSCLC. In vitro assay indicated that down-regulation of circ_0067934 could suppress NSCLC cells proliferation, migration, and invasion. Mechanistic analysis showed that aberrant circ_0067934 expression could modulate the expression levels of markers of epithelial-to-mesenchymal transition. Conclusions Our data suggested that circ_0067934 functioned as an oncogenic circular RNA in NSCLC, which provided a potential prognostic biomarker and therapeutic target for NSCLC.

CircRNA circ_0067934 silencing inhibits the proliferation, migration and invasion of NSCLC cells and correlates with unfavorable prognosis in NSCLC.

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CircRNA circ_0067934 silencing inhibits the proliferation, migration and invasion of NSCLC cells and correlates with unfavorable prognosis in NSCLC.