RNA sequencing analysis of miR-603 overexpression

Alzheimer’s disease (AD) is a serious neurodegenerative disease in which miRNAs have been linked to its pathogenesis. miR-603 is a primate-specific miRNA. Through ADNI data analysis, we found a SNP rs11014002 in pre-miR-603 which promotes the biogenesis of mature miR-603 is associated with AD risk. We further identified that LRPAP1, a protein which antagonizes the function of LRP1 in Aß clearance and AD susceptibility, is a target gene of miR-603. Moreover, overexpression of miR-603 increased the protein level of LRP1, suggesting the protective role of miR-603 in AD. Both significant increase and loss of regulatory function of miR-603 hint the existence of a compensatory mechanism in hippocampus of AD subjects. Furthermore, we found that miR-603 could directly downregulate E2F1 and prevent cells from H2O2 induced-apoptosis. This work provides the first evidence that miR-603 may modulate AD susceptibility and the SNP rs11014002 (T-carrier genotype) might be a protective factor for AD. Overall design: There are two groups: Negative Control and miR-603 overexpression. We performed experiments on HEK293 cell and Hela cell.