Int Neurourol J.
2018 Dec;22(4):237-245. 10.5213/inj.1836274.137.
Comprehensive MicroRNAome Analysis of the Relationship Between Alzheimer Disease and Cancer in PSEN Double-Knockout Mice
- Affiliations
-
- 1Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology (KIST), Seoul, Korea. him@kist.re.kr
- 2Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul, Korea.
- 3Department of Pharmacology, Seoul National University College of Medicine, Seoul, Korea.
- 4Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
- 5Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, Korea.
- KMID: 2431864
- DOI: http://doi.org/10.5213/inj.1836274.137
Abstract
- PURPOSE
Presenilins are functionally important components of γ-secretase, which cleaves a number of transmembrane proteins. Manipulations of PSEN1 and PSEN2 have been separately studied in Alzheimer disease (AD) and cancer because both involve substrates of γ-secretase. However, numerous clinical studies have reported an inverse correlation between AD and cancer. Interestingly, AD is a neurodegenerative disorder, whereas cancer is characterized by the proliferation of malignant cells. However, this inverse correlation in the PSEN double-knockout (PSEN dKO) mouse model of AD has been not elucidated, although doing so would shed light onto the relationship between AD and cancer.
METHODS
To investigate the inverse relationship of AD and cancer under conditions of PSEN loss, we used the hippocampus of 7-month-old and 18-month-old PSEN dKO mice for a microRNA (miRNA) microarray analysis, and explored the tumorsuppressive or oncogenic role of differentially-expressed miRNAs.
RESULTS
The total number of miRNAs that showed changes in expression level was greater at 18 months of age than at 7 months. Most of the putative target genes of the differentially-expressed miRNAs involved Cancer pathways.
CONCLUSIONS
Based on literature reviews, many of the miRNAs involved in Cancer pathways were found to be known tumorsuppressive miRNAs, and their target genes were known or putative oncogenes. In conclusion, the expression levels of known tumor-suppressive miRNAs increased at 7 and 18 months, in the PSEN dKO mouse model of AD, supporting the negative correlation between AD and cancer.
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