Estrogen receptor alpha (ERα) regulates PARN-mediated nuclear deadenylation and gene expression in breast cancer cells

Varriano, Sophia; Yu, Amy; Xu, Yu Qing; Natelson, Devorah M.; Ramadei, Anthony; Kleiman, Frida E.

doi:10.1080/15476286.2024.2413821

RNA Biology

2024

DOI: 10.1080/15476286.2024.2413821

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Estrogen receptor alpha (ERα) regulates PARN-mediated nuclear deadenylation and gene expression in breast cancer cells

Sophia Varriano,

Amy Yu,

Yu Qing Xu

et al.

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2024

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In Silico Discovery of Multi-Target Natural Ligands and Efficient siRNA Design for Overcoming Drug Resistance in Breast Cancer via Local Therapy

Hashemi,

Barzegar,

Akhtari

et al. 2024

Preprint

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In this study, we designed an efficient siRNA for PKMYT1 gene knockdown, and evaluated the binding affinities of different natural ligands to crucial proteins involved in breast cancer. Designed siRNA showed strong binding affinity and minimal off-target effects. Molecular docking studies identified new ligands as antagonists with high binding affinities for aromatase, estrogen receptor alpha, HER2, and PARP10, as well as agonists for MT2 and STING. The natural ligand SCHEMBL7562664 was introduced as a golden ligand due to its high affinity among multiple targets and lack of cytotoxic and mutagenic effects. Natural small molecules identified in this research, due to their multi-target characteristics, provided a solution to overcome the problem of drug resistance in cancer cells. Furthermore, the proposed three dimensional scaffold design for local breast cancer therapy offers a promising approach to increase the delivery and efficacy of these natural small molecules, reduce systemic side effects, and improve treatment outcomes. In this study, new ligands with significant binding affinities and favorable pharmacokinetic properties were identified, which paves the way for further research in targeted therapy of breast cancer.

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In Silico Discovery of Multi-Target Natural Ligands and Efficient siRNA Design for Overcoming Drug Resistance in Breast Cancer via Local Therapy

Hashemi,

Barzegar,

Akhtari

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

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Estrogen receptor alpha (ERα) regulates PARN-mediated nuclear deadenylation and gene expression in breast cancer cells

Cited by 1 publication

References 44 publications

In Silico Discovery of Multi-Target Natural Ligands and Efficient siRNA Design for Overcoming Drug Resistance in Breast Cancer via Local Therapy

In Silico Discovery of Multi-Target Natural Ligands and Efficient siRNA Design for Overcoming Drug Resistance in Breast Cancer via Local Therapy

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