A New Discovery of MicroRNA-455-3p in Alzheimer's Disease

Abstract

MicroRNA-455-3p (miR-455-3p) is identify as a member of broadly conserved miRNA family expressed in most of the phylum and species. In humans, miR-455 is present on the human chromosome 9 at locus 9q32 and encoded by the human COL27A1 gene (collagen type XXVII alpha 1 chain). The role of miR-455 has been implicated in various human diseases such as cartilage development, adipogenesis, preeclampsia, and cancers, e.g., colon cancer, prostate cancer, hepatocellular carcinoma, renal cancer, oral squamous cancer, skin cancer, and non-small cell lung cancer. Recently, our laboratory discovered the biomarker and therapeutic relevance of miR-455-3p in Alzheimer's disease (AD). Our global microarray analysis of serum samples from AD patients, mild cognitive individuals (MCI), and healthy subjects unveiled the high level of miR-455-3p in AD patients relative to MCI and healthy controls. Further, validation analysis using different kinds of AD samples such as serum, postmortem brains, AD fibroblasts, AD B-lymphocytes, AD cell lines, AD mouse models, and AD cerebrospinal fluid confirmed the biomarker potential of miR-455-3p. The mechanistic link of miR-455-3p in AD was determined via modulation of amyloid-β protein precursor (AβPP) and amyloid-β (Aβ) levels. Luciferase reporter assay confirmed AβPP as validated target of miR-455-3p. Our study on mouse neuroblastoma cells revealed the protective role of miR-455-3p against Aβ-induced toxicities. We also noticed that miR-455-3p enhances cell survival and lifespan extension. High level of miR-455-3p reduces Aβ toxicity, enhances mitochondrial biogenesis and synaptic activity, and maintains healthy mitochondrial dynamics. Based on these evidences, we cautiously conclude that miR-455-3p is a promising peripheral biomarker and therapeutic candidate for AD.