Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2

By W. Du, Weining Yang, E. Liu, Zhenguo Yang, P. Dhaliwal, Burton B. Yang. Nucleic Acids Research, 2016

1,487 citations recorded by the source corpus.

Most RNAs generated by the human genome have no protein-coding ability and are termed non-coding RNAs. Among these include circular RNAs, which include exonic circular RNAs (circRNA), mainly found in the cytoplasm, and intronic RNAs (ciRNA), predominantly detected in the nucleus. The biological functions of circular RNAs remain largely unknown, although ciRNAs have been reported to promote gene transcription, while circRNAs may function as microRNA sponges. We demonstrate that the circular RNA circ-Foxo3 was highly expressed in non-cancer cells and were associated with cell cycle progression. Silencing endogenous circ-Foxo3 promoted cell proliferation. Ectopic expression of circ-Foxo3 repressed cell cycle progression by binding to the cell cycle proteins cyclin-dependent kinase 2 (also known as cell division protein kinase 2 or CDK2) and cyclin-dependent kinase inhibitor 1 (or p21), resulting in the formation of a ternary complex. Normally, CDK2 interacts with cyclin A and cyclin E to facilitate cell cycle entry, while p21works to inhibit these interactions and arrest cell cycle progression. The formation of this circ-Foxo3-p21-CDK2 ternary complex arrested the function of CDK2 and blocked cell cycle progression.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/6d616f2498e3e9cbb2506d332280f09e5619caae

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Citations in the corpus

Circular RNA cSMARCA5 inhibits growth and metastasis in hepatocellular carcinoma. (2018, background): “In fact, many studies have proved that circRNAs can function as sponges for microRNAs (miRNAs) [13-20] or bind to proteins[21, 22], and altered circRNA levels can result in aberrant expression of gene products that may contribute to cancer”
Induction of tumor apoptosis through a circular RNA enhancing Foxo3 activity (2016, methodology): “The methods for protein precipitating RNA and RNA pull-down proteins were performed as described.(11)”
Circular RNA and its mechanisms in disease: From the bench to the clinic. (2018, background): “, 2015; Kelly, Greenman, Cook, & Papantonis, 2015), and these circRNAs are dynamically regulated among tissues and cell types (Du et al., 2016; Li, Chen, et al., 2015).”
Past, present, and future of circRNAs (2019, neutral): “These hairpins are bound by RBPs responsible for intracellular immune response.”
Circular RNA-protein interactions: functions, mechanisms, and identification (2020, methodology): “In brief [44], cell cultures are washed in ice-cold phosphate-buffered saline and lysed in co-IP buffer, followed by incubation with biotinylated DNA oligo probes at room temperature.”
Circular RNAs: Promising Biomarkers for Human Diseases (2018, background): “Circ-Foxo3 can repress cell cycle progression by binding to G1 to S phase transitionrelated CDK2 and p21 [24].”
Circ-ZNF609 Is a Circular RNA that Can Be Translated and Functions in Myogenesis (2017, background): “, 2014), and to circ-Foxo3, which blocks cell-cycle progression by interacting with Cdk (Du et al., 2016).”
CSCD: a database for cancer-specific circular RNAs (2017, background): “Another potential function of circRNAs is that circRNA serves as sponges for RNA-binding proteins (RBPs) (41).”
Circular RNA: metabolism, functions and interactions with proteins (2020, background): “This impedes the formation of CDK2/cyclin E and CDK2/cyclin A complexes, and thus blocks G1/S transition and S progression, respectively, ultimately leading to cell cycle arrest in G1 phase [93].”
CircRNA: functions and properties of a novel potential biomarker for cancer (2017, background): “More circRNA functions were also found, such as acting as scaffolds in the assembly of protein complexes [3], sequestering proteins from their native subcellular localization [4], modulating the expression of parental genes [5–8], regulating alternative splicing [9] and RNA–protein interactions [10]”
Circular RNA circMTO1 acts as the sponge of microRNA‐9 to suppress hepatocellular carcinoma progression (2017, background): “circRNAs may regulate the expression of oncogenic or tumor suppressive genes through different targets, depending on the different types of cancer or even at different stages.((35)) The most reported function pattern for circRNAs is acting as a miRNA sponge and forming the circRNA-miRNAmRNA axis.”
Novel Role of FBXW7 Circular RNA in Repressing Glioma Tumorigenesis (2017, background): “CircRNAs are novel RNA molecules with different biological functions and pathological implications (10,37,38).”
CircRNA: a novel type of biomarker for cancer (2017, background): “Circ-Foxo3 acts on p21 and CDK2 to form circ-Foxo3– p21–CDK2 ternary complex which hinders the combination between CDK2 and cyclin E, which hinders cell transition from G1 into S phase [65].”