Ozfiliz-Kilbas Pelin, Sonmez Ozlem, Obakan-Yerlikaya Pinar, Coker-Gurkan Ajda, Palavan-Ünsal Narcin, Uysal-Onganer Pinar, Arisan Elif Damla
Department of Molecular Biology and Genetics, Istanbul Kultur University, Istanbul 34158, Turkey.
Department of Biomedical Engineering, Biruni University, Istanbul 34010, Turkey.
Cancers (Basel). 2021 Oct 23;13(21):5322. doi: 10.3390/cancers13215322.
(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.
(1) 背景：脂肪酸合成增加会导致乳腺癌的侵袭性表型并降低治疗效果。脂质生物合成途径上的调控性微小RNA（miRNA）如miR-33a有可能阐明确切机制。(2) 方法：我们在非细胞毒性浓度下，将MCF-7和MDA-MB-231乳腺癌细胞暴露于雌激素受体（ER）激活剂（雌二醇-17β，E2）或抗雌激素药物（ICI 182,780，氟维司群，FUL）后，测定miR-33a的表达水平。我们通过免疫印迹将细胞中miR-33a的表达水平与细胞脂质生物合成相关途径联系起来。(3) 结果：在存在雌二醇-17β（E2）或氟维司群（FUL）的情况下，miR-33a模拟物处理导致MCF-7细胞中脂肪酸合酶（FASN）显著下调，但在MDA-MB-231细胞中未出现这种情况。与miR-33a抑制剂的作用相反，miR-33a模拟物与E2或FUL共转染导致MCF-7细胞中AMP激活的蛋白激酶α（AMPKα）活性降低。无论细胞内miR-33a水平如何，E2都会增加MDA-MB-231细胞中的FASN水平。miR-33a抑制剂联合处理可抑制E2介导的MDA-MB-231细胞中AMPKα的活性。(4) 结论：miR-33a的细胞表达水平对于理解包括细胞能量传感器如AMPKα激活状态在内的乳腺癌细胞差异反应至关重要。
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