circ-ZNF609: A potent circRNA in human cancers

Abstract

Circular RNAs (circRNAs) are a novel group of endogenous RNAs with a circular structure. Growing evidence indicates that circRNAs are involved in a variety of human diseases including malignancies. CircRNA ZNF609 (circ-ZNF609), derived from the ZNF609 gene sequence, has been demonstrated to be involved in the development and progression of many diseases. circ-ZNF609 is thought to be a viable diagnostic and prognostic biomarker for several diseases and might be a new therapeutic target, but further research is needed to accelerate clinical application. Here, we review the biogenesis and function of circRNAs and the functional roles and molecular mechanism related to circ-ZNF609 in neoplasms and other diseases.

Keywords: cancers; circ-ZNF609; circular RNAs; microRNA sponge; review.

FIGURE 1

Biogenesis and conservation of circ‐ZNF609. The smaller boxes represented the 5′ and 3′ UTRs while the larger boxes indicated the Coding sequences (CDS). Start codons are shown in green while stop codons are shown in red. circ‐ZNF609 (right) originates from ZNF609 mRNA (above), ZNF609 pre‐mRNA (centre) and ZNF609 s exon (below)

FIGURE 2

Biogenesis of circRNAs. CircRNAs are generated from lariat‐driven circulation or back‐splicing events. (Three main mechanisms: intron pairing‐driven circularization, RBPs‐mediated circularization and lariat‐driven circularization). RBPs, RNA‐binding proteins

FIGURE 3

Functions of circRNAs. CircRNAs can act as biomarkers (A), miRNAs sponges (B), be combined with RBPs (C), Act as templates for protein translation (D). Abbreviations: circRNAs, circular RNAs. miRNAs, microRNAs. RBPs, RNA‐binding proteins

FIGURE 4

circ‐ZNF609 mediates mechanisms involved in cancer progression. (RCC) circ‐ZNF609 could upregulate the expression of FOXP4 by sponging miR‐138‐5p. (Nasopharyngeal carcinoma) circ‐ZNF609 may act as a ceRNA to sponge miR‐150‐5p, miR‐338‐3p or miR‐145‐5p to promote the expression of SP1, HRAS or STMN1. (Gastric cancer) circ‐ZNF609 could bind to miR‐145‐5p. (Lung cancer) circ‐ZNF609 can promote ETV1, FOXM1 or GNB2 signal pathway through sponging miR‐1224‐3p, miR‐623 or miR‐142‐3p. (Hepatocellular carcinoma) circ‐ZNF609 could promote RAP2C expression via serving as sponge of miR‐342‐3p. (Prostate cancer) circ‐ZNF609 could sponge miR‐501‐3p to promote the HK2 expression. (Cervical cancer) circ‐ZNF609 may promote the expression of E2F6 via binding to miR‐197‐3p. (Glioma) circ‐ZNF609 upregulated the PLK1 expression by sponging miR‐1224‐3p. (Colorectal cancer) circ‐ZNF609 may promote Gli1 signal pathway through sponging miR‐150‐5p. FOXP4, forkhead box P4. HRAS, HRas proto‐oncogene, GTPase. STMN1, stathmin 1. ETV1, ets variant gene 1. FOXM1, forkhead box M1. GNB2, G protein subunit beta 2. HK2, hexokinase 2. E2F6, E2F transcription factor 6. PLK1, Polo‐like Kinase 1

FIGURE 5

circ‐ZNF609 mediates mechanisms involved in human non‐malignant diseases progression. (Hirschsprung) circ‐ZNF609 could upregulate the expression of AKT3 by sponging miR‐150‐5p. (Vascular endothelial dysfunction and Glaucoma) circ‐ZNF609 upregulated the MEF2A and METRN expression by sponging miR‐615‐5p. (Corneal neovascularization) circ‐ZNF609 may promote the expression of AKT and VEGF via binding to miR‐184. (Neuropathic pain) circ‐ZNF609 may promote ENO1 signal pathway through sponging miR‐22‐3p. AKT3, AKT serine/threonine kinase 3. MEF2A, myocyte enhancer factor 2A. METRN, meteorin. ENO1, enolase 1