Dose-Dependent Downregulation of miR-335-5p in Response to Tamoxifen Reveals a PIAS4–ESR1 Regulatory Axis in Breast Cancer Cells

Senem Noyan; Yasemin Öztemur Islakoğlu

doi:10.17776/csj.1932689

Dose-Dependent Downregulation of miR-335-5p in Response to Tamoxifen Reveals a PIAS4–ESR1 Regulatory Axis in Breast Cancer Cells

Abstract

Breast cancer remains the most frequently diagnosed cancer among women worldwide, and estrogen receptor–positive (ER+) tumors are primarily treated with endocrine therapies; however, resistance to agents such as tamoxifen limits treatment efficacy. MicroRNAs (miRNAs) have emerged as pivotal regulatory molecules in breast cancer, offering promising avenues for both therapeutic intervention and prognostic evaluation. In this study, we investigated the role of miR-335-5p in response to tamoxifen and trastuzumab and explored its regulatory relationship with ESR1, NRIP1, and PIAS4. ER-positive (ER+) breast cancer cells were transfected with miR-335-5p mimic or scrambled control and treated with tamoxifen at IC50 and IC70 concentrations. Gene and miRNA expression levels were assessed using qRT-PCR, and protein expression was evaluated by Western blotting. Bioinformatics analyses, including target prediction, correlation analyses, and drug response datasets, were integrated to support the findings. Our results indicate that miR-335-5p regulates ESR1 and NRIP1 expression indirectly through PIAS4, a negative regulator of these genes. This interaction is consistent with the observed positive correlation between miR-335-5p and its downstream targets. Collectively, these findings suggest a dose-dependent role of miR-335-5p in modulating endocrine therapy response and identify a previously uncharacterized miR-335–ESR1–PIAS4 regulatory axis in ER+ breast cancer.

Keywords

Endocrine therapy, ESR1, NRIP1, miR-335-5p, Tamoxifen

Ethical Statement

This study was conducted using established cell lines and did not involve human participants or animals. Therefore, ethical approval was not required.

References

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Details

Primary Language

English

Subjects

Cancer Biology, Epigenetics

Journal Section

Research Article

Authors

Senem Noyan ^*
0000-0001-6455-3702
Türkiye

Yasemin Öztemur Islakoğlu
0000-0001-7792-7777
Türkiye

Publication Date

October 27, 2026

Submission Date

April 17, 2026

Acceptance Date

September 7, 2026

Published in Issue

Year 2026 Volume: 47 Number: 5

DOI

https://doi.org/10.17776/csj.1932689

IZ

https://izlik.org/JA92XF77SU

APA

Noyan, S., & Öztemur Islakoğlu, Y. (2026). Dose-Dependent Downregulation of miR-335-5p in Response to Tamoxifen Reveals a PIAS4–ESR1 Regulatory Axis in Breast Cancer Cells. Cumhuriyet Science Journal, 47(5), 829-838. https://doi.org/10.17776/csj.1932689

AMA

1.Noyan S, Öztemur Islakoğlu Y. Dose-Dependent Downregulation of miR-335-5p in Response to Tamoxifen Reveals a PIAS4–ESR1 Regulatory Axis in Breast Cancer Cells. CSJ. 2026;47(5):829-838. doi:10.17776/csj.1932689

Chicago

Noyan, Senem, and Yasemin Öztemur Islakoğlu. 2026. “Dose-Dependent Downregulation of MiR-335-5p in Response to Tamoxifen Reveals a PIAS4–ESR1 Regulatory Axis in Breast Cancer Cells”. Cumhuriyet Science Journal 47 (5): 829-38. https://doi.org/10.17776/csj.1932689.

EndNote

Noyan S, Öztemur Islakoğlu Y (October 1, 2026) Dose-Dependent Downregulation of miR-335-5p in Response to Tamoxifen Reveals a PIAS4–ESR1 Regulatory Axis in Breast Cancer Cells. Cumhuriyet Science Journal 47 5 829–838.

IEEE

[1]S. Noyan and Y. Öztemur Islakoğlu, “Dose-Dependent Downregulation of miR-335-5p in Response to Tamoxifen Reveals a PIAS4–ESR1 Regulatory Axis in Breast Cancer Cells”, CSJ, vol. 47, no. 5, pp. 829–838, Oct. 2026, doi: 10.17776/csj.1932689.

ISNAD

Noyan, Senem - Öztemur Islakoğlu, Yasemin. “Dose-Dependent Downregulation of MiR-335-5p in Response to Tamoxifen Reveals a PIAS4–ESR1 Regulatory Axis in Breast Cancer Cells”. Cumhuriyet Science Journal 47/5 (October 1, 2026): 829-838. https://doi.org/10.17776/csj.1932689.

JAMA

1.Noyan S, Öztemur Islakoğlu Y. Dose-Dependent Downregulation of miR-335-5p in Response to Tamoxifen Reveals a PIAS4–ESR1 Regulatory Axis in Breast Cancer Cells. CSJ. 2026;47:829–838.

MLA

Noyan, Senem, and Yasemin Öztemur Islakoğlu. “Dose-Dependent Downregulation of MiR-335-5p in Response to Tamoxifen Reveals a PIAS4–ESR1 Regulatory Axis in Breast Cancer Cells”. Cumhuriyet Science Journal, vol. 47, no. 5, Oct. 2026, pp. 829-38, doi:10.17776/csj.1932689.

Vancouver

1.Senem Noyan, Yasemin Öztemur Islakoğlu. Dose-Dependent Downregulation of miR-335-5p in Response to Tamoxifen Reveals a PIAS4–ESR1 Regulatory Axis in Breast Cancer Cells. CSJ. 2026 Oct. 1;47(5):829-38. doi:10.17776/csj.1932689

As of 2026, Cumhuriyet Science Journal will be published in six issues per year, released in February, April, June, August, October, and December

Dose-Dependent Downregulation of miR-335-5p in Response to Tamoxifen Reveals a PIAS4–ESR1 Regulatory Axis in Breast Cancer Cells

Abstract

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Ethical Statement

References

Details

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