Cellular origin of miR-21 and miR-145 in prostate cancer. A reappraisal of their putative function in carcinogenesis

Since their discovery, micro-RNAs (miRNA) have raised wide interest as potential biomarkers for a host of diseases. These short strands of RNA, which do not code for protein, play an important role in the regulation of protein expression, by their ability to bind to complementary sequences on specific mRNA and thus suppress its translation. Several miRNAs, which have been detected in blood or tissue homogenates, have been shown to correlate significantly with the presence of prostate cancer, or with the risk of developing a tumor at a later stage, or with the subsequent course of the disease in patients with an established cancer diagnosis [1]. However, published reports are often contradictory. Putative biomarkers that are based on a statistical correlation without an understanding of their biological origin may not necessarily reflect a direct connection with the underlying pathological process. RNA is produced inside cells, and in a solid tissue consisting of several cell types, individual miRNA sequences may be produced in certain cells and not in others, perhaps under particular conditions of cellular physiology. This aspect of miRNA-biology cannot be addressed by analysis of biological fluids or tissue homogenates, a simple fact which is all too often overlooked in current literature.