MicroRNAs as Novel Biomarkers for Breast Cancer

Abstract

Breast cancer is a complex phenotypically diverse genetic disease, involving a variety of changes in gene expression and structure. Recent advances in molecular profiling technology have made great progress in unravelling the molecular taxonomy of breast cancer, which has shed new light on the aetiology of the disease and also heralded great potential for the development of novel biomarkers and therapeutic targets. Mi(cro)RNAs are a contemporary class of small noncoding endogenous RNA molecules, generating great excitement in the clinical and scientific communities. The recent discovery that miRNA expression is frequently dysregulated in cancer has uncovered an entirely new repertoire of molecular factors upstream of gene expression, which warrants extensive investigation to further elucidate their precise role in malignancy. We present a comprehensive and timely review of the role of miRNAs in cancer: addressing miRNA function, their putative role as oncogenes or tumor suppressors, with a particular emphasis on breast cancer throughout. We discuss the recent discovery of quantifiable circulating cancer-associated miRNAs, which heralds immense potential for their use as novel minimally invasive biomarkers for breast and other cancers. Finally, we comment on the potential role of miRNAs in breast cancer management, particularly in improving current prognostic tools and achieving the goal of individualized cancer treatment.

Deregulated Serum Concentrations of Circulating Cell–Free MicroRNAs miR-17, miR-34a, miR-155, and miR-373 in Human Breast Cancer Development and Progression

“…Based on their binding affinity to hundreds of different mRNAs, they are involved in the regulation of various cellular processes (5 ). Because miR loci frequently map to fragile chromosomal regions harboring DNA amplifications, deletions, or translocations, their expression is often deregulated during tumorigenesis and contributes to tumor progression (6,7 ). MiRs are released into the blood circulation by apoptotic and necrotic cells (8 ) as well as by active secretion in small particles, such as exosomes.…”

Impaired Biomechanical Properties of Diabetic Skin

“…36 Alternatively, studies have demonstrated that lack of microRNA production can permit uncontrolled cellular proliferation in the setting of leukemia 37 and breast cancer. 38 Recently, Roggli et al 39 demonstrated in a mouse diabetic model that inflammatory cytokines elicit production of microRNA species that may be involved in the development of pancreatic ␤-cell failure, whereas the direct connection between increased production of microRNA targeting collagen gene expression and diabetes is still unclear. This pathophysiology can certainly explain our findings, but of course, more investigation is necessary of to further evaluate the role microRNA species play in the development of diabetes.…”

Intracellular and Extracellular MicroRNAs in Breast Cancer

“…As with many cancers, progress in early breast cancer detection has been inadequate (4 ), and methods for determining diagnosis and prognosis of breast cancer are still limited to invasive procedures, such as tissue biopsies for histological examination (5,6 ). Advances in understanding the cancer cell at the molecular level have enabled development of several targeted therapies that have advanced the treatment of relevant patient subgroups.…”