Lower Serum Levels of miR-29c-3p and miR-19b-3p as Biomarkers for Alzheimer’s Disease

Abstract

MicroRNAs (miRNAs) are short noncoding RNA that participate in posttranscriptional gene regulation. However, little is understood about the roles of miRNAs in Alzheimer's disease (AD). In this study, we used next-generation sequencing on RNA extracted from the serum samples of 20 AD patients and 20 controls, yielding a total of 72 miRNAs with significantly changed expression levels. Among these candidates, we selected 9 miRNAs with most significant alteration in disease, and validated their expression levels using RT-qPCR analysis on serum samples from 45 AD patients and 40 control subjects. Thus, the serum levels of miR-146a-5p, 106b-3p, 195-5p, 20b-5p, and 497-5p were significantly higher, while those of miR-125b-3p, 29c-3p, 93-5p and 19b-3p were significantly lower in AD patients, compared with control subjects. Two miRNAs, miR-29c-3p and miR-19b-3p, were selected because both RNA deep-sequencing and q-PCR methods indicated lower serum levels of these miRNAs in AD patients. Computational analysis predicted that 3′-untranslated region of signal transduction and activator of transcription 3 (STAT3) mRNA is targeted both by miR-29c-3p and miR-19b-3p. Using SH-SY5Y human neuroblastoma cells, we showed that transfection with miR-29c-3p or miR-19b-3p inhibitor significantly increased STAT3 phosphorylation. Furthermore, Water maze test, which assesses the learning and memory deficits in rodents, showed that escape latency was significantly shorter in AD rats with overexpression of miR-29c-3p or miR-19b-3p than in control AD rats. These results suggest that miR-29c-3p or miR-19b-3p may contribute to the cognitive function. In conclusion, the serum levels of miR-29c-3p and miR-19b-3p are helpful biomarkers for AD.

Exercise – induced changes in cerebrospinal fluid miRNAs in Gulf War Illness, Chronic Fatigue Syndrome and sedentary control subjects

“…Diminished miR-186-3p allows increased BACE1 mRNA translation and cleavage of amyloid peptides that increase the risk for brain disease. miR-19b-3p was reduced in serum from Alzheimer’s patients, and targeted signal transduction and activator of transcription 3 (STAT3) mRNA in a murine model 50 . miR-92a-3p was increased in glioblastoma and targeted BCL2L11 to reduce tumor apoptosis 51 .…”

Clinical significance of miR-19b-3p in patients with sepsis and its regulatory role in the LPS-induced inflammatory response

“…In a study of acute myocardial infarction (AMI), circulating miR-19b-3p was consider to be a promising biomarker for the early phase of AMI [25]. Another study in Alzheimer's disease (AD) indicated that miR-19b-3p was determined to be lower in the serum of AD patients, and the serum level of miR-19b-3p might be a helpful biomarker for AD diagnosis [26]. For sepsis, a variety of abnormally expressed miRNAs have been identified to be associated with the development and progression of sepsis, such as miR-21 and miR-26b [9,10].…”

MicroRNAs miR-19, miR-340, miR-374 and miR-542 regulate MID1 protein expression

“…Furthermore, we have observed increased expression of MID1 in Alzheimer’s disease brains [ 74 ]. Our data showing that miR-19b-3p targets MID1 provide one possible explanation for increased expression of MID1 in Alzheimer’s disease tissue, that may be caused by reduced levels of miR-19b-3p [ 72 , 75 ]. Future studies should address if miRNA based therapeutics such as miRNA mimics of the four MID1-targeting miRNAs hsa-miR-19b-3p, hsa-miR-340-5p, hsa-miR-374a-5p and hsa-miR-542-3p could be used to downregulate MID1 in Alzheimer’s disease models and thereby counteract formation of amyloid plaques.…”