<i>ZNF703</i> mRNA-Targeting Antisense Oligonucleotide Blocks Cell Proliferation and Induces Apoptosis in Breast Cancer Cell Lines
Sandra Udu-Ituma,
José Adélaïde,
Thi Khanh Le,
Kenneth Omabe,
Pascal Finetti,
Clément Paris,
Arnaud Guille,
François Bertucci,
Daniel Birnbaum,
Palma Rocchi,
Max Chaffanet
Affiliations
Sandra Udu-Ituma
Equipe Labellisée Ligue Nationale Contre le Cancer, Predictive Oncology Laboratory, Marseille Research Cancer Center, INSERM U1068, CNRS U7258, Institut Paoli-Calmettes, Aix Marseille University, 13009 Marseille, France
José Adélaïde
Equipe Labellisée Ligue Nationale Contre le Cancer, Predictive Oncology Laboratory, Marseille Research Cancer Center, INSERM U1068, CNRS U7258, Institut Paoli-Calmettes, Aix Marseille University, 13009 Marseille, France
Thi Khanh Le
Equipe Labellisée Ligue Nationale Contre le Cancer, Predictive Oncology Laboratory, Marseille Research Cancer Center, INSERM U1068, CNRS U7258, Institut Paoli-Calmettes, Aix Marseille University, 13009 Marseille, France
Kenneth Omabe
Equipe Labellisée Ligue Nationale Contre le Cancer, Predictive Oncology Laboratory, Marseille Research Cancer Center, INSERM U1068, CNRS U7258, Institut Paoli-Calmettes, Aix Marseille University, 13009 Marseille, France
Pascal Finetti
Equipe Labellisée Ligue Nationale Contre le Cancer, Predictive Oncology Laboratory, Marseille Research Cancer Center, INSERM U1068, CNRS U7258, Institut Paoli-Calmettes, Aix Marseille University, 13009 Marseille, France
Clément Paris
Equipe Labellisée Ligue Nationale Contre le Cancer, Predictive Oncology Laboratory, Marseille Research Cancer Center, INSERM U1068, CNRS U7258, Institut Paoli-Calmettes, Aix Marseille University, 13009 Marseille, France
Arnaud Guille
Equipe Labellisée Ligue Nationale Contre le Cancer, Predictive Oncology Laboratory, Marseille Research Cancer Center, INSERM U1068, CNRS U7258, Institut Paoli-Calmettes, Aix Marseille University, 13009 Marseille, France
François Bertucci
Equipe Labellisée Ligue Nationale Contre le Cancer, Predictive Oncology Laboratory, Marseille Research Cancer Center, INSERM U1068, CNRS U7258, Institut Paoli-Calmettes, Aix Marseille University, 13009 Marseille, France
Daniel Birnbaum
Equipe Labellisée Ligue Nationale Contre le Cancer, Predictive Oncology Laboratory, Marseille Research Cancer Center, INSERM U1068, CNRS U7258, Institut Paoli-Calmettes, Aix Marseille University, 13009 Marseille, France
Palma Rocchi
Equipe Labellisée Ligue Nationale Contre le Cancer, Predictive Oncology Laboratory, Marseille Research Cancer Center, INSERM U1068, CNRS U7258, Institut Paoli-Calmettes, Aix Marseille University, 13009 Marseille, France
Max Chaffanet
Equipe Labellisée Ligue Nationale Contre le Cancer, Predictive Oncology Laboratory, Marseille Research Cancer Center, INSERM U1068, CNRS U7258, Institut Paoli-Calmettes, Aix Marseille University, 13009 Marseille, France
The luminal B molecular subtype of breast cancers (BC) accounts for more than a third of BCs and is associated with aggressive clinical behavior and poor prognosis. The use of endocrine therapy in BC treatment has significantly contributed to the decrease in the number of deaths in recent years. However, most BC patients with prolonged exposure to estrogen receptor (ER) selective modulators such as tamoxifen develop resistance and become non-responsive over time. Recent studies have implicated overexpression of the ZNF703 gene in BC resistance to endocrine drugs, thereby highlighting ZNF703 inhibition as an attractive modality in BC treatment, especially luminal B BCs. However, there is no known inhibitor of ZNF703 due to its nuclear association and non-enzymatic activity. Here, we have developed an antisense oligonucleotide (ASO) against ZNF703 mRNA and shown that it downregulates ZNF703 protein expression. ZNF703 inhibition decreased cell proliferation and induced apoptosis. Combined with cisplatin, the anti-cancer effects of ZNF703-ASO9 were improved. Moreover, our work shows that ASO technology may be used to increase the number of targetable cancer genes.
