Lessons from microRNA biology: Top key cellular drivers of Autosomal Dominant Polycystic Kidney Disease

Numerous microRNAs (miRs), small RNAs targeting several pathways, have been implicated in the development of Autosomal Dominant Polycystic Kidney Disease (ADPKD), which is the most common genetic cause of Chronic Kidney Disease. The hallmark of ADPKD is tissue overgrowth and hyperproliferation, eventually leading to kidney failure. Many miRs are dysregulated in disease, yet the intracellular pathways regulated by these are less well described in ADPKD. Here, I summarise all the differentially expressed miRs and highlight the top miR-regulated cellular driver of ADPKD. Literature review has identified 35 abnormally expressed miRs in ADPKD. By performing bioinformatics analysis of their target genes I present 10 key intracellular pathways that drive ADPKD progression. The top key drivers are divided into three main areas: (i) hyperproliferation and the role of JAK/STAT and PI3K pathways (ii) DNA damage and (iii) inflammation and NFκB. The description of the 10 top cellular drivers of ADPKD, derived by analysis of miR signatures, is of paramount importance in better understanding the key processes resulting in pathophysiological changes that underlie disease. • A hallmark of Autosomal Dominant Polycystic Kidney Disease (ADPKD) is excessive proliferation • MicroRNAs alter cellular signaling and contribute to ADPKD progression • Ten top Hallmark pathways were derived using microRNA-gene interaction signatures • Inflammation (NFκB), DNA damage (p53) and proliferation (STAT5 & PI3K) are discussed in this review.