Downregulation of GJA1-Derived circ_753 and circ_755 Differentially Modulates miR-182-5p Expression and Breast Cancer-Associated Phenotypes
4 affiliations
- 1Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Beirut 1107 2020, Lebanon
- 2Institut de Cancérologie de l’Ouest, 49055 Angers, France
- 3Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon
- 4Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon
Abstract
CircRNAs are key regulators of gene expression. The functional roles of exonic versus exon–intron circRNAs in early breast cancer remain unclear. Connexin-43 (GJA1) generates exonic circRNA (ecircRNA) hsa_circ_0077755 (circ_755) and exon–intron circRNA (EIcircRNA), hsa_circ_0077753 (circ_753), both linked to increased breast cancer risk. We examined their structural, molecular, and phenotypic roles in transient and stable knockdown S1 breast epithelial cells, using RT-qPCR, dual-luciferase, lumen formation and invasion assays, and extracellular vesicle (EV) analysis. Knockdown of cytoplasm-enriched circ_755 reduced Connexin-43 transcript and protein, whereas knockdown of nuclear-enriched circ_753 preserved GJA1. Both induced lumen disruption, β-catenin disorganization, increased invasion, and regulated onco-miR-182. More pronounced miR-182 upregulation and broader repression of tumor-suppressive targets (BCL2, FOXO1, RECK) were observed in circ_753 knockdown cells, alongside concurrent depletion of hsa_circ_0008932 (circ_8932), which is predicted to interact with miR-182. Similar reciprocal changes in circRNA/miR-182 were observed in released EVs. These data highlight circRNA-miR-182 networks with distinct effects on tumor initiation and potential value as breast cancer biomarkers.
Related
- The obesity associated BDNF intron-3 cis-regulatory element, BE5.1, modulates the effects of early-life stress on weight gain, anxiety and gene expression in a sex dependent manner.
- Luteolin potentiates antibiotic activity against multidrug-resistant Pseudomonas aeruginosa and modulates efflux-associated resistance and biofilm-associated phenotypes
- G3BP1 reduction during cellular senescence promotes SVIL expression and selected senescence-associated phenotypes
- VIRMA-associated SRD5A2 downregulation promotes BPH progression through ERα-CREB5-dependent epithelial plasticity
- KH1 Domain of Poly C Binding Protein 1 (PCBP1) Interacts with Utrophin-A mRNA and Modulates Utrophin-A Expression in Mouse Myoblasts
BibTeX
@article{maatouk2026downregulation,
title = {{Downregulation of GJA1-Derived circ_753 and circ_755 Differentially Modulates miR-182-5p Expression and Breast Cancer-Associated Phenotypes}},
author = {Nour Maatouk and Joséphine Briand and Jana Ismael and Serena Andraos and Abdallah Kurdi and Sophie Lelièvre and Rihab Nasr and Rabih Talhouk},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27198849},
url = {https://www.mdpi.com/1422-0067/27/19/8849},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Downregulation of GJA1-Derived circ_753 and circ_755 Differentially Modulates miR-182-5p Expression and Breast Cancer-Associated Phenotypes
AU - Nour Maatouk
AU - Joséphine Briand
AU - Jana Ismael
AU - Serena Andraos
AU - Abdallah Kurdi
AU - Sophie Lelièvre
AU - Rihab Nasr
AU - Rabih Talhouk
PY - 2026
DA - 2026/10/03
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27198849
UR - https://www.mdpi.com/1422-0067/27/19/8849
AB - CircRNAs are key regulators of gene expression. The functional roles of exonic versus exon–intron circRNAs in early breast cancer remain unclear. Connexin-43 (GJA1) generates exonic circRNA (ecircRNA) hsa_circ_0077755 (circ_755) and exon–intron circRNA (EIcircRNA), hsa_circ_0077753 (circ_753), both linked to increased breast cancer risk. We examined their structural, molecular, and phenotypic roles in transient and stable knockdown S1 breast epithelial cells, using RT-qPCR, dual-luciferase, lumen formation and invasion assays, and extracellular vesicle (EV) analysis. Knockdown of cytoplasm-enriched circ_755 reduced Connexin-43 transcript and protein, whereas knockdown of nuclear-enriched circ_753 preserved GJA1. Both induced lumen disruption, β-catenin disorganization, increased invasion, and regulated onco-miR-182. More pronounced miR-182 upregulation and broader repression of tumor-suppressive targets (BCL2, FOXO1, RECK) were observed in circ_753 knockdown cells, alongside concurrent depletion of hsa_circ_0008932 (circ_8932), which is predicted to interact with miR-182. Similar reciprocal changes in circRNA/miR-182 were observed in released EVs. These data highlight circRNA-miR-182 networks with distinct effects on tumor initiation and potential value as breast cancer biomarkers.
SN - 1422-0067
ER -