Metabolism-regulating non-coding RNAs in breast cancer: roles, mechanisms and clinical applications

Abstract

Breast cancer is one of the most common malignancies that pose a serious threat to women's health. Reprogramming of energy metabolism is a major feature of the malignant transformation of breast cancer. Compared to normal cells, tumor cells reprogram metabolic processes more efficiently, converting nutrient supplies into glucose, amino acid and lipid required for malignant proliferation and progression. Non-coding RNAs(ncRNAs) are a class of functional RNA molecules that are not translated into proteins but regulate the expression of target genes. NcRNAs have been demonstrated to be involved in various aspects of energy metabolism, including glycolysis, glutaminolysis, and fatty acid synthesis. This review focuses on the metabolic regulatory mechanisms and clinical applications of metabolism-regulating ncRNAs involved in breast cancer. We summarize the vital roles played by metabolism-regulating ncRNAs for endocrine therapy, targeted therapy, chemotherapy, immunotherapy, and radiotherapy resistance in breast cancer, as well as their potential as therapeutic targets and biomarkers. Difficulties and perspectives of current targeted metabolism and non-coding RNA therapeutic strategies are discussed.

Keywords: Amino acid metabolism; Breast cancer; Glycolysis; Lipid metabolism; Metabolism; Non-coding RNAs.

Fig. 1

Characterization, biogenesis and biology of ncRNAs. Biogenesis of miRNAs, LncRNAs, circRNAs and tsRNAs and the molecular mechanisms of their biological functions

Fig. 2

Steps in ncRNA-regulated reprogramming of glucose metabolism in breast cancer by glycolysis, lactate formation, glycogen synthesis and catabolism and the tricarboxylic acid cycle. Blue boxes and arrows represent positive regulations, while red boxes and lines with blunt ends represent negative regulations

Fig. 3

Steps in ncRNA-regulated reprogramming of fatty acid synthesis, β-oxidation, cholesterol synthesis and phospholipid metabolism in breast cancer. Blue boxes and arrows represent positive regulations, while red boxes and lines with blunt ends represent negative regulations. Dashed lines indicate omitted steps

Fig. 4

Steps in ncRNA-regulated reprogramming of amino acid metabolism. Blue boxes and arrows represent positive regulations, while red boxes and lines with blunt ends represent negative regulations

Fig. 5

Clinical implications of non-coding RNAs and metabolism in breast cancer