In Vitro Investigations of miR-33a Expression in Estrogen Receptor-Targeting Therapies in Breast Cancer Cells

Pelin Ozfiliz-Kilbas; Ozlem Sonmez; Pinar Obakan-Yerlikaya; Ajda Coker-Gurkan; Narcin Palavan-Ünsal; Pinar Uysal-Onganer; Elif Damla Arisan

doi:10.3390/cancers13215322

In Vitro Investigations of miR-33a Expression in Estrogen Receptor-Targeting Therapies in Breast Cancer Cells

Cancers (Basel). 2021 Oct 23;13(21):5322. doi: 10.3390/cancers13215322.

Authors

Pelin Ozfiliz-Kilbas¹, Ozlem Sonmez¹, Pinar Obakan-Yerlikaya², Ajda Coker-Gurkan³, Narcin Palavan-Ünsal⁴, Pinar Uysal-Onganer⁵, Elif Damla Arisan⁶

Affiliations

¹ Department of Molecular Biology and Genetics, Istanbul Kultur University, Istanbul 34158, Turkey.
² Department of Biomedical Engineering, Biruni University, Istanbul 34010, Turkey.
³ Department of Molecular Biology and Genetics, Biruni University, Istanbul 34010, Turkey.
⁴ Department of Engineering, Netkent Mediterranean Research and Science University, 38-44 Kyrenia, Macka 99300, Turkey.
⁵ Cancer Research Group, School of Life Sciences, University of Westminster, London W1W 6UW, UK.
⁶ Institute of Biotechnology, Gebze Technical University, Gebze 41400, Turkey.

Abstract

(1) Background: Increased fatty acid synthesis leads to the aggressive phenotype of breast cancer and renders efficiency of therapeutics. Regulatory microRNAs (miRNAs) on lipid biosynthesis pathways as miR-33a have potential to clarify the exact mechanism. (2) Methods: We determined miR-33a expression levels following exposure of MCF-7 and MDA-MB-231 breast cancer cells to estrogen receptor (ER) activator (estradiol-17β, E2) or anti-estrogens (ICI 182,780, Fulvestrant, FUL) at non-cytotoxic concentrations. We related miR-33a expression levels in the cells to cellular lipid biosynthesis-related pathways through immunoblotting. (3) Results: miR-33a mimic treatment led to significantly downregulation of fatty acid synthase (FASN) in MCF-7 cells but not in MDA-MB-231 cells in the presence of estradiol-17β (E2) or Fulvestrant (FUL). In contrast to the miR-33a inhibitor effect, miR-33a mimic co-transfection with E2 or FUL led to diminished AMP-activated protein kinase α (AMPKα) activity in MCF-7 cells. E2 increases FASN levels in MDA-MB-231 cells regardless of miR-33a cellular levels. miR-33a inhibitor co-treatment suppressed E2-mediated AMPKα activity in MDA-MB-231 cells. (4) Conclusions: The cellular expression levels of miR-33a are critical to understanding differential responses which include cellular energy sensors such as AMPKα activation status in breast cancer cells.

Keywords: FASN; adipogenesis; breast cancer; estrogen; fulvestrant; miR-33a.