Circular RNA-mediated miRNA sponge & RNA binding protein in biological modulation of breast cancer

Abstract

Circular RNAs (circRNAs) and small non-coding RNAs of the head-to-junction circle in the construct play critical roles in gene regulation and are significantly associated with breast cancer (BC). Numerous circRNAs are potential cancer biomarkers that may be used for diagnosis and prognosis. Widespread expression of circRNAs is regarded as a feature of gene expression in highly diverged eukaryotes. Recent studies show that circRNAs have two main biological modulation models: sponging and RNA-binding. This review explained the biogenesis of circRNAs and assessed emerging findings on their sponge function and role as RNA-binding proteins (RBPs) to better understand how their interaction alters cellular function in BC. We focused on how sponges significantly affect the phenotype and progression of BC. We described how circRNAs exercise the translation functions in ribosomes. Furthermore, we reviewed recent studies on RBPs, and post-protein modifications influencing BC and provided a perspective on future research directions for treating BC.

Keywords: Biogenesis; Breast cancer; CircRNAs; RNA-Binding proteins (RBPs); Sponge.

Fig. 1

I:CircRNAs contribute to regulate BC and induce kinds of phenotypes including proliferation, metasatasis, invasion,EMT, apoptosis and cell cycle. Canonical signaling pathways as NOTCH1, PI3K/Akt, Wnt, Hippo and EMT were activated by circRNAs. CircRNAs were investigated to act as sponges and compete endogenous with miRNAs to regulate BC progression.

Fig. 2

II:CircRNAs promote chemotherapies drug resistance, for axample, ADM,OX,DOX.

Fig. 3

III: Apoptosis is a cell death process activated by inflammasome sensors and culminates in the loss of plasma membrane integrity. CircRNAs induce cell apoptosis of BC.

Fig. 4

IV: CircRNAs regulate cell cycle in BC, however, mainly in G1/S stage.

Fig. 5

Sankey diagram of circRNAs, E3 ubiquitin ligase and function in BC. USP10 is one of the key E3 ubiquitin ligase which be found a proliferation promotor enzyme for BC and an induction of tube formation of human umbilical vein endothelial cells.

Fig. 6

A: CircRNAs act as sponge to affect BC proression. B. I: m⁶A induces methylation activities and comprises two individual proteins: methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14). II: Ubiquitin is the progression that E1 catalyzes the formation of a covalent thioester bond between the catalytic cysteine and the di-glycine motif on the C-terminus of ubiquitin by a magnesium ion and ATP and is delivered to E2. E3 binds to E2 ubiquitin and facilitates binding to the target protein. III: Tyrosine kinase, MAP kinase, cadherin-catenin complex, and cyclin-dependent kinase are major players in the cell cycle and deregulation of phosphorylation-dephosphorylation cascade. C: CircRNAs were detected the internal ribosome entry site (IRES) to facilitate cap-independent translation.