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. 2019 Oct 25;110(12):3630–3638. doi: 10.1111/cas.14211

Figure 3.

Figure 3

Biological functions of cancer‐suppressive circular RNAs (circRNAs). A, Acting as a sponge of microRNA (miRNA). For example, circ_000911 competitively binds with miR‐449a, which binds with Argonaute 2 (Ago2) and targets notch homolog 1 (Notch 1) mRNA. B, Interacting with proteins. For example, circNOL10 first binds with sex comb on midleg‐like 1 (SCML1), then moves transcription factor binding sites (TFBS), and finally promotes the expression of human protein (HN) in lung cancer. C, Translating proteins. For example, the pre‐mRNA of F‐box and WD repeat domain containing 7 (FBXW7) may produce a circRNA called circFBXW7 and FBXW7α mRNA. The open reading frame (ORF) in circFBXW7, which is driven by the internal ribosome entry site, encodes a protein, FBXW7‐185aa. FBXW7‐185aa can bind with ubiquitin‐specific peptidase 28 (USP28) to prevent USP28 binding with FBXW7α mRNA, thereby reducing the half‐life of c‐Myc and reducing the stability of c‐Myc. D, Regulating the transcription of linear RNA. For example, the pre‐mRNA of zinc finger protein with KRAB and SCAN domains 1 (ZKSCAN1) may produce a circRNA called circZKSCAN1 that acts as a competitive inhibitor to retain endogenous RNA and then regulates the expression of cell proliferation and apoptosis‐related genes, including apoptotic genes RAS‐associated C3 botulinum toxin substrate 2 (RAC2), ephrin‐A3 (EFNA3), and caspase 3, transforming growth factor beta 1 (TGFB1), integrin beta 4 (ITGB4), and CXC motif chemokine receptor 4 (CXCR4)