title: MicroRNA-153 negatively regulates the expression of amyloid precursor protein and amyloid precursor-like protein 2.
abstract: Increased expression of the amyloid precursor protein (APP) is a crucial risk factor of Alzheimer's disease (AD). Amyloid precursor-like protein 2 (APLP2), a homologue of APP, is also suggested to participate in AD pathogenesis. Accumulating evidence suggest the regulatory role of microRNA on AD-related genes. Here we showed that the levels of miR-153 were significantly decreased at early- and late-stage of AD in APPswe/PSΔE9 murine model. Moreover, a binding site of miR-153 on APP and APLP2-3'UTR was identified, respectively, by luciferase assay. Gain and loss of function experiments demonstrated that miR-153 suppressed the expression of APP and APLP2. Using miR-153 transgenic mouse model, we testified that miR-153 downregulated the expression of APP and APLP2 protein in vivo. Furthermore, closely related expression patterns of miR-153 and APP/APLP2 during brain development indicated a physiological regulation role of miR-153 on the two genes. In a neuronal cell line treated with Aβ(42) peptides and H(2)O(2,) the levels of miR-153 varied during time-course leading to corresponding changes of APLP2 protein, indicating Aβ peptides and oxidative stress influence the expression of miR-153. Thus, miR-153 contributes to post-transcriptional regulation of APP/APLP2, suggesting a possible role for miR-153 in neuro-pathological conditions.
authors.affiliation: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medical Center, Peking Union Medical College, PR China.
authors.forename: Chunlian
authors.initials: C
authors.lastname: Liang
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Xu
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
authors.forename: Chunmei
authors.initials: C
authors.lastname: Ma
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000502:physiology*
chemical_list: D016564:Amyloid beta-Protein Precursor; C492952:Aplp2 protein, mouse; C577878:MIRN153 microRNA, mouse; D035683:MicroRNAs