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.

Figure 1

MiRNA biogenesis and processing in human cells: the multistep process begins in the nucleus where the RNase III enzyme Drosha, coupled with its binding partner DGCR8, cleaves nascent miRNA transcripts (pri-miRNA) into ~70 nucleotide precursors (pre-miRNA). These pre-miRNAs consist of an imperfect stem-loop structure. Pre-miRNAs are then exported from the nucleus into the cytoplasm by Exportin 5. In the cytoplasm, the hairpin precursors are cleaved by Dicer and its binding partner the transactivator RNA-binding protein TRBP into a small, imperfect dsRNA duplex (miRNA : miRNA*) that contains both the mature miRNA strand and its complementary strand. The miRNA strand is incorporated into the miRNP complex and targets complementary mRNA sequences, exerting its functionality via mRNA cleavage or translational repression.