Multiple Layers of CDK5R1 Regulation in Alzheimer's Disease Implicate Long Non-Coding RNAs

International Journal of Molecular Sciences
Marco SpreaficoMarco Venturin

Abstract

Cyclin-dependent kinase 5 regulatory subunit 1 (CDK5R1) gene encodes for p35, the main activator of Cyclin-dependent kinase 5 (CDK5). The active p35/CDK5 complex is involved in numerous aspects of brain development and function, and its deregulation is closely associated to Alzheimer's disease (AD) onset and progression. We recently showed that miR-15/107 family can negatively regulate CDK5R1 expression modifying mRNA stability. Interestingly, miRNAs belonging to miR-15/107 family are downregulated in AD brain while CDK5R1 is upregulated. Long non-coding RNAs (lncRNAs) are emerging as master regulators of gene expression, including miRNAs, and their dysregulation has been implicated in the pathogenesis of AD. Here, we evaluated the existence of an additional layer of CDK5R1 expression regulation provided by lncRNAs. In particular, we focused on three lncRNAs potentially regulating CDK5R1 expression levels, based on existing data: NEAT1, HOTAIR, and MALAT1. We demonstrated that NEAT1 and HOTAIR negatively regulate CDK5R1 mRNA levels, while MALAT1 has a positive effect. We also showed that all three lncRNAs positively control miR-15/107 family of miRNAs. Moreover, we evaluated the expression of NEAT1, HOTAIR, and MALAT1 in AD and...Continue Reading

References

Jan 24, 2007·The European Journal of Neuroscience·Jian-Zhi WangKhalid Iqbal
Apr 3, 2007·Neuroscience Letters·Claudie HooperRichard Killick
Jun 27, 2007·Journal of Cell Science·Jong-Hee LeeKyong-Tai Kim
May 29, 2010·Genome Biology·Mohammad Ali FaghihiClaes Wahlestedt
Jun 25, 2010·Cold Spring Harbor Perspectives in Biology·Archa H Fox, Angus I Lamond
Jul 10, 2010·Science·Miao-Chih TsaiHoward Y Chang
Mar 2, 2011·Nature Neuroscience·James R TollerveyJernej Ule
Jan 10, 2012·Cold Spring Harbor Perspectives in Medicine·Alberto Serrano-PozoBradley T Hyman
Jun 6, 2012·Annual Review of Biochemistry·John L Rinn, Howard Y Chang
Mar 27, 2013·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Tony GutschnerSven Diederichs
Nov 1, 2013·Molecular Biology of the Cell·Tetsuro HiroseGérard Pierron
Dec 18, 2013·Human Molecular Genetics·Tatyana A ShelkovnikovaVladimir L Buchman
Jun 27, 2014·Seminars in Cell & Developmental Biology·Je-Hyun YoonMyriam Gorospe
Aug 27, 2014·Molecular Cell·Jason A WestRobert E Kingston
Jul 1, 2012·Brain Disorders & Therapy·Kristina A McLindenEdward Giniger
Nov 22, 2014·Nature Communications·Dimple ChakravartyMark A Rubin
Mar 20, 2015·BioMed Research International·Teng JiangJin-Tai Yu
May 31, 2015·Advanced Drug Delivery Reviews·O KhorkovaC Wahlestedt
Aug 1, 2015·Molecular Neurobiology·Shu-Lei LiuJin-Tai Yu
Aug 5, 2015·Molecular Medicine Reports·Xin Yu, Zheng Li
Dec 29, 2015·Molecular Medicine Reports·Ying Li, Xin Wang
Jan 30, 2016·Journal of Experimental & Clinical Cancer Research : CR·Peng WangLingmei Qu
Mar 16, 2016·International Journal of Molecular Sciences·Ahmed S BayoumiIl-Man Kim
May 25, 2016·Zhongguo fei ai za zhi = Chinese journal of lung cancer·Haitian ZhangLin Xu
May 26, 2016·Molecular Neurobiology·Jun-Sang SunwooManho Kim
Jun 25, 2016·Current Alzheimer Research·Paola RivaMarco Venturin
Jun 18, 2017·Current Medicinal Chemistry·Claus DeslerLene Juel Rasmussen
Jul 13, 2017·Genes & Development·Stephano S MelloLaura D Attardi
Aug 29, 2017·Nature Structural & Molecular Biology·Li JiangXiang-Dong Fu

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Citations

Apr 9, 2020·Journal of Biomedical Science·Yi-Ying Wu, Hung-Chih Kuo
Mar 19, 2020·Metabolic Brain Disease·Shamseddin AhmadiSteven Bradburn
Feb 28, 2020·Scientific Reports·Taesic Lee, Hyunju Lee
Dec 20, 2020·International Journal of Molecular Sciences·Leticia Moreno-GarcíaRosario Osta
Mar 23, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Finn McCluggage, Archa H Fox
May 25, 2021·Journal of Alzheimer's Disease : JAD·Guan-Yong OuWei-Jiang Zhao

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Methods Mentioned

BETA
antisense oligonucleotides
transfection
PCR
Assay
PCRs

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