Mechanistic Role of MicroRNA in Cancer Chemoprevention by Nonsteroidal Anti-inflammatory Drugs

Abstract

Over the past several decades, studies have documented the cancer chemopreventive activity of nonsteroidal anti-inflammatory drugs (NSAIDs) by lowering incidence and slowing down progression of malignant disease, which consequently lead to decline of cancer-related mortality and improvement of disease progression-free survival (PFS). Inhibition of cyclooxygenase (COX) has been primarily believed to be the key mechanism responsible for anticancer activity of NSAIDs, while the serious toxicity caused by COX inhibitory effect reduces the enthusiasm to use NSAIDs as chemopreventive agents in the clinic. Recently, more and more studies demonstrate that non-COX inhibitory mechanisms may, at least partially, account for anticancer properties of NSAIDs, which potentially support the indication of NSAIDs on cancer chemoprevention. MicroRNAs (miRNAs) are a set of non-coding and small RNA molecules with the master regulatory effect on over 30 % human genes through the post-transcriptional and translational modulation. Although miRNAs have been reported to be involved in many normal and pathological processes including cell proliferation, apoptosis, differentiation, as well as tumorigenesis; their roles in NSAIDs’ properties of cancer chemoprevention have not yet been studied exclusively. Here, we will review the prior studies reporting the interactions between miRNAs and COX/non-COX pathways with the intent to provide new insights into the molecular mechanisms responsible for NSAIDs’ anticancer activity.