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Review
. 2024 Apr 26;21(3):213-237.
doi: 10.21873/cgp.20442.

Deregulated circRNAs in Epithelial Ovarian Cancer With Activity in Preclinical In Vivo Models: Identification of Targets and New Modalities for Therapeutic Intervention

Ulrich H Weidle  1 , Fabian Birzele  2
Affiliations
Review

Deregulated circRNAs in Epithelial Ovarian Cancer With Activity in Preclinical In Vivo Models: Identification of Targets and New Modalities for Therapeutic Intervention

Ulrich H Weidle et al. Cancer Genomics Proteomics. .

Abstract

Epithelial ovarian cancer (EOC) is associated with a dismal prognosis due to development of resistance to chemotherapy and metastasis in the peritoneal cavity and distant organs. In order to identify new targets and treatment modalities we searched the literature for up- and and down-regulated circRNAs with efficacy in preclinical EOC-related in vivo systems. Our search yielded circRNAs falling into the following categories: cisplatin and paclitaxel resistance, transmembrane receptors, secreted factors, transcription factors, RNA splicing and processing factors, RAS pathway-related components, proteolysis and cell-cycle regulation, signaling-related proteins, and circRNAs regulating proteins in additional categories. These findings can be potentially translated by validation and manipulation of the corresponding targets, inhibition of circRNAs with antisense oligonucleotides (ASO), small interfering RNAs (siRNA) or small hairpin RNA (shRNA) or by reconstituting their activity.

Keywords: Inhibition and reconstitution of circ RNA; review; small hairpin RNA (shRNA); small interfering RNA (siRNA); target validation; xenograft models.

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Conflict of interest statement

FB is and UHW was an employee of Roche.

Figures

Figure 1
Figure 1. circRNAs involved in cisplatin resistance of epithelial ovarian cancer with efficacy in preclinical in vivo models. circRNAs mediating cisplatin resistance are shown. Upward arrows indicate up-regulation, and downward arrows indicate down-regulation. CHTOP: Chromatin target of CHTOP; circCDRas: circ cerebellar degenerated-related protein 1 antisense; HIPK2: circ homeodomain containing protein kinase 2; circITGB6: circ integrin β6; circLAPR3: circ lysophosphatic acid receptor 3; circSNX12: circ sorting nexin 12; CLU: clusterin; DDP: cisplatin; FGF9: fibroblast growth factor 9; miR: micro RNA; DNAJB6: DNA homolog subfamily B, member 6; KLF4: Krueppel-like factor 4; PDK1: pyruvate dehydrogenase kinase 1; PPA-1: inorganic pyrophosphatase 1; PPP1R12B: protein phosphatase 1 regulatory subunit 12B; RAB1A: ras-related protein RAB1A; SCL7A11: solute carrier family 7, member 11.
Figure 2
Figure 2. circRNAs involved in paclitaxel resistance of epithelial ovarian cancer with efficacy in preclinical in vivo models. CircRNAs mediating paclitaxel resistance are shown. Up-ward arrows indicate up-regulation, downward arrows correlate with down-regulation. CBX2: Chromobox 2; circANKRD17: circ ankyrin repeat domain 17; circCELSR1: circ cadherin EGF LAG receptor seven-pass G-type receptor 1; EXO6B: circ exocyst complex component 6B; circNRIP1: circ nuclear receptor interacting protein 1; circSETDB1: circ bifurcated lysine methyltransferase 1; circTNPO3: circ transportin 3; FOXO3: forkhead box protein O3; FOXR2: forkhead box 2; HOXC8: homeobox C8; miR: micro RNA; NEK2: never in mitosis (NIMA) related kinase 2; P-GP: P-glycoprotein; PTX: paclitaxel; SIK2: salt-induced kinase 2.
Figure 3
Figure 3. circRNAs regulating transmembrane receptors and secreted factors of epithelial ovarian cancer with efficacy in preclinical in vivo models. Upward arrows indicate up-regulation, downward arrows correlate with down-regulation. circASHL2: circ histone lysine methyltransferase 2L; circITCH: circ Itchy homolog; circKLF4: circ kinesin family member 4A; circRHOC: circ RAS homology family member C; circWHSC1: circ Wolf- Hirschhorn syndrome candidate 1; CADH1: cadherin 1; FZD4: frizzled 4; hTERT: human telomerase reverse transcriptase; JAM3: junctional adhesion molecule 3; LETM1: leucine zipper and EF-hand transmembrane protein 1; M: metastasis; miR: micro RNA; MUC1: mucin 1; PLXNB2: plexin B2; SLC1A5: solute carrier 1A5; SFRP1: secreted frizzled related protein 1; TG: tumor growth.
Figure 4
Figure 4. circRNAs regulating transcription factors, RNA binding and splicing factors and RAS pathway-related factors with activity in preclinical in vivo models of epithelial ovarian cancer. Upward arrows indicate up-regulation, downward arrows correlate with down-regulation. CHD1L: Chromosomal helicase DNA binding protein; circBCN2: circ basonuclin 2; circCERS6: circ ceramide synthase 6; circCRIM1: circ cysteine rid motor neuron protein 1; circITCH: Itchy homolog ubiquitin protein ligase; circPTK2: circ protein tyrosine kinase 2; FOXC1: forkhead box C1; FOXM1: forkhead box M1; IGF2BP2: insulin growth factor binding protein 2; LARP4: La ribonucleoprotein 4; LSM4: Sm-like protein 4; MEX3C: Mex-3 RNA binding family member C; miR: micro RNA; RAB1A: RAS-related protein RAB1A; RASA1: RAS p21 protein activator 1; RASSF8: RASassociated domain family nuclear 8; TG: tumor growth; ZEB2: zinc finger E-box homeo box 2.
Figure 5
Figure 5. circRNAs regulating ubiquitinylation and cell-cycle related factors of epithelial ovarian cancer with efficacy in preclinical in vivo models. Upward arrows indicate up-regulation, and downward arrows indicate down-regulation. CDC5L: Cell-division 5-like; CDK6: cyclin-dependent kinase 6; circBCN2: circ basonuclin 2; circPGAM1: circ phosphoglycerate mutase 1; circSETDB1: circ SET domain bifurcated lysine methyltransferase 1; Cul 4B: cullin 4B; DUSP5: dual specificity phosphatase 5; FBXW7: F box and WD repeat domain containing 7; M: metastasis; MAPK3K3: mitogen-related protein kinase kinase kinase 3; miR: micro-RNA; TG: tumor growth.
Figure 6
Figure 6. circRNAs regulating signaling and factors of other categories of epithelial ovarian cancer with efficacy in preclinical in vivo models. Upward arrows indicate up-regulation, and downward arrows indicate down-regulation. BRCA1: Breast cancer related antigen 1; circATP2B4: circ ATPase plasma membrane Ca2+ transporter 4; circAHNAK: circ neuroblast differentiation associated gene AHNAK; circATRNL1: circ attractinlike 1; circKRT7: circ keratin 7; circPLEKM3: pleckstrin homology domain family member 3; COL1A1: collagen 1A1; DNAJB6; DNA J heat shock family (hsp40) member B6; EIF2B5: eucaryotic initiation factor 2B, subunit ε; EZH2: enhancer of zeste homolog 2; M: metastasis; miR: micro RNA; PSAT1: phosphoserine aminotransferase 1; PTEN: phosphatase and tensin homolog; ROCK1: RHO-associated protein kinase 1; SMAD4: decapentaplegic homolog 4; SOCS3: suppressor of cytokine signaling 3; SREBF1: sterol regulatory element binding factor 1; TG: tumor growth.
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