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

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.

Oestrogen receptor positive breast cancer and its embedded mechanism: breast cancer resistance to conventional drugs and related therapies, a review

“…miR-33a is one of the miRNAs reported in BC drug resistance. It inhibits gene ABCA1 expression and also hinders cholesterol reverse transport in High-density Lipoprotein (HDL) [67,98]. miR-33a activates AMPKα which further activates the transcription of genes responsible for ATP production [99].…”

“…miR-33a is one of the miRNAs reported in BC drug resistance. It inhibits gene ABCA1 expression and also hinders cholesterol reverse transport in High-density Lipoprotein (HDL) [ 67 , 98 ].…”

“…miR-33a activates AMPKα which further activates the transcription of genes responsible for ATP production [ 99 ]. This miRNA expression has been shown to cause fulvestrant resistance in the cell line of triple-negative breast cancer (TNBC) [ 98 ]. All these changes cause radiation-resistant BC [ 67 ].…”

Decoding the regulatory roles of non-coding RNAs in cellular metabolism and disease

“… 148 Similarly, miR-33a mimic treatment suppressed the expression of FASN in breast cancer cells ( Figure 5 and Table S2 ). 149 …”

Implication of microRNAs in Carcinogenesis with Emphasis on Hematological Malignancies and Clinical Translation

“…In recent years, implication of miRNAs in the metabolic reprogramming of tumor cells has been confirmed, including the regulation of glycolysis, glutaminolysis and anabolic pathways, such as miR-210, miR-23a, and miR-33a, respectively [ 77 , 78 ]. According to the latest data, impaired expression of miR-652-5p leads to decreased levels of ATP, lactate, and pyruvate in T-ALL cell lines, thereby providing a potential drug target [ 79 ].…”