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

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Ozfiliz-Kilbas P., Sonmez O., Obakan-Yerlikaya P., Coker-Gurkan A., Palavan-Unsal N., Uysal-Onganer P., ...Daha Fazla

CANCERS, cilt.13, sa.21, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 13 Sayı: 21
  • Basım Tarihi: 2021
  • Doi Numarası: 10.3390/cancers13215322
  • Dergi Adı: CANCERS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, CINAHL, EMBASE, Veterinary Science Database, Directory of Open Access Journals
  • Anahtar Kelimeler: estrogen, breast cancer, miR-33a, adipogenesis, FASN, fulvestrant, 17-BETA-ESTRADIOL, STATISTICS, METABOLISM, MICRORNAS, OBESITY
  • Marmara Üniversitesi Adresli: Hayır

Özet

Simple Summary:& nbsp;Altered metabolic pathways determine the aggressivity of breast cancer cells. To highlight the potential markers gains importance to understand early molecular signatures of disease. microRNAs are the small non-coding RNAs found in different biological samples. Due to the dysregulation of metabolic pathways, the expression and secretion of microRNAs are modulated.
(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-17 beta, 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-17 beta (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 a (AMPKa) 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 AMPKa 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 AMPKa activation status in breast cancer cells.