Obesity as a Risk Factor for Breast Cancer—The Role of miRNA

Abstract

Breast cancer (BC) is the most common cancer diagnosed among women in the world, with an ever-increasing incidence rate. Due to the dynamic increase in the occurrence of risk factors, including obesity and related metabolic disorders, the search for new regulatory mechanisms is necessary. This will help a complete understanding of the pathogenesis of breast cancer. The review presents the mechanisms of obesity as a factor that increases the risk of developing breast cancer and that even initiates the cancer process in the female population. The mechanisms presented in the paper relate to the inflammatory process resulting from current or progressive obesity leading to cell metabolism disorders and disturbed hormonal metabolism. All these processes are widely regulated by the action of microRNAs (miRNAs), which may constitute potential biomarkers influencing the pathogenesis of breast cancer and may be a promising target of anti-cancer therapies.

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“…Relative to our subject, there are breast cancer-associated miRNAs (upregulation of miR-20, downregulation of miR-46), obesity-related miRNAs (upregulation of miR-23, downregulation of miR-14), miRNAs common to breast cancer and obesity (let-7, miR-21, -30c, -31, -93, -124, -143, -155, -181a, -221/222, -326, 335), and miRNAs common in breast cancer and obesity-associated breast cancer (upregulation of miR-302b, downregulation of miR-498) 37 . MiRNAs also have different functions: some are related to tumor suppression (i.e., let-7, -200, -205, -145) and are downregulated in the context of breast cancer, some serve as oncogenic signal (miR-10, -17, -21, -155) and are upregulated in breast tumorigenesis, and some propagate metastasis (miR-9, -36, -10b, -37, -38, -21, -39-45, -29a, -46, -373/520) 38 , 39 .…”

“…The key players for orchestrating all these processes and secreting pivotal molecules are adipose tissue-derived mesenchymal stromal/stem cells (ASCs/MSCs) 42 , 43 . The alterations that these mechanisms bring upon, under the influence of single-nucleotide polymorphisms (SNPs) and epigenetic modifications (obesogenic dietary patterns, unhealthy foods, sedentary lifestyle and lack of exercise), affect all stages of tumorigenesis, including initiation, progression, migration, invasion, and metastasis 28 , 30 , 38 , 39 , 44 .…”