Xiaoping Tan1, Yang Liu1, Taiming Zhang1, Shuyan Cong2. 1. Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, 36 Sanhao Street, Shenyang, 110004, Liaoning, People's Republic of China. 2. Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, 36 Sanhao Street, Shenyang, 110004, Liaoning, People's Republic of China. whenshan524@163.com.
Abstract
BACKGROUND: Huntington's disease (HD) is one of the most common polyglutamine disorders, leading to progressive dyskinesia, cognitive impairment, and neuropsychological problems. Besides the dysregulation of many protein-coding genes in HD, previous studies have revealed a variety of non-coding RNAs that are also dysregulated in HD, including several long non-coding RNAs (lncRNAs). However, an integrated analysis of differentially expressed (DE) genes based on a competing endogenous RNA (ceRNA) network is still currently lacking. METHODS: In this study, we have systematically analyzed the gene expression profile data of neural progenitor cells (NPCs) derived from patients with HD and controls (healthy controls and the isogenic controls of HD patient cell lines corrected using a CRISPR-Cas9 approach at the HTT locus) to screen out DE mRNAs and DE lncRNAs and create a ceRNA network. To learn more about the possible functions of lncRNAs in the ceRNA regulatory network in HD, we conducted a functional analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) and established a protein-protein interaction (PPI) network for mRNAs interacting with these lncRNAs. RESULTS: We identified 490 DE mRNAs and 94 DE lncRNAs, respectively. Of these, 189 mRNAs and 20 lncRNAs were applied to create a ceRNA network. The results showed that the function of DE lncRNAs mainly correlated with transcriptional regulation as demonstrated by GO analysis. Also, KEGG enrichment analysis showed these lncRNAs were involved in tumor necrosis factor, calcium, Wnt, and NF-kappa B signaling pathways. Interestingly, the PPI network revealed that a variety of transcription factors in the ceRNA network interacted with each other, suggesting such lncRNAs may regulate transcription in HD by controlling the expression of such protein-coding genes, especially transcription factors. CONCLUSIONS: Our research provides new clues for uncovering the mechanisms of lncRNAs in HD and can be used as the focus for further investigation.
BACKGROUND:Huntington's disease (HD) is one of the most common polyglutamine disorders, leading to progressive dyskinesia, cognitive impairment, and neuropsychological problems. Besides the dysregulation of many protein-coding genes in HD, previous studies have revealed a variety of non-coding RNAs that are also dysregulated in HD, including several long non-coding RNAs (lncRNAs). However, an integrated analysis of differentially expressed (DE) genes based on a competing endogenous RNA (ceRNA) network is still currently lacking. METHODS: In this study, we have systematically analyzed the gene expression profile data of neural progenitor cells (NPCs) derived from patients with HD and controls (healthy controls and the isogenic controls of HDpatient cell lines corrected using a CRISPR-Cas9 approach at the HTT locus) to screen out DE mRNAs and DE lncRNAs and create a ceRNA network. To learn more about the possible functions of lncRNAs in the ceRNA regulatory network in HD, we conducted a functional analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) and established a protein-protein interaction (PPI) network for mRNAs interacting with these lncRNAs. RESULTS: We identified 490 DE mRNAs and 94 DE lncRNAs, respectively. Of these, 189 mRNAs and 20 lncRNAs were applied to create a ceRNA network. The results showed that the function of DE lncRNAs mainly correlated with transcriptional regulation as demonstrated by GO analysis. Also, KEGG enrichment analysis showed these lncRNAs were involved in tumor necrosis factor, calcium, Wnt, and NF-kappa B signaling pathways. Interestingly, the PPI network revealed that a variety of transcription factors in the ceRNA network interacted with each other, suggesting such lncRNAs may regulate transcription in HD by controlling the expression of such protein-coding genes, especially transcription factors. CONCLUSIONS: Our research provides new clues for uncovering the mechanisms of lncRNAs in HD and can be used as the focus for further investigation.
Authors: Andrew S Yoo; Alfred X Sun; Li Li; Aleksandr Shcheglovitov; Thomas Portmann; Yulong Li; Chris Lee-Messer; Ricardo E Dolmetsch; Richard W Tsien; Gerald R Crabtree Journal: Nature Date: 2011-07-13 Impact factor: 49.962
Authors: Blair R Leavitt; Jeremy M van Raamsdonk; Jacqueline Shehadeh; Herman Fernandes; Zoe Murphy; Rona K Graham; Cheryl L Wellington; Lynn A Raymond; Michael R Hayden Journal: J Neurochem Date: 2006-01-17 Impact factor: 5.372
Authors: Miao-Chih Tsai; Ohad Manor; Yue Wan; Nima Mosammaparast; Jordon K Wang; Fei Lan; Yang Shi; Eran Segal; Howard Y Chang Journal: Science Date: 2010-07-08 Impact factor: 47.728
Authors: Mitchell Guttman; Ido Amit; Manuel Garber; Courtney French; Michael F Lin; David Feldser; Maite Huarte; Or Zuk; Bryce W Carey; John P Cassady; Moran N Cabili; Rudolf Jaenisch; Tarjei S Mikkelsen; Tyler Jacks; Nir Hacohen; Bradley E Bernstein; Manolis Kellis; Aviv Regev; John L Rinn; Eric S Lander Journal: Nature Date: 2009-02-01 Impact factor: 49.962
Authors: Angela Hodges; Andrew D Strand; Aaron K Aragaki; Alexandre Kuhn; Thierry Sengstag; Gareth Hughes; Lyn A Elliston; Cathy Hartog; Darlene R Goldstein; Doris Thu; Zane R Hollingsworth; Francois Collin; Beth Synek; Peter A Holmans; Anne B Young; Nancy S Wexler; Mauro Delorenzi; Charles Kooperberg; Sarah J Augood; Richard L M Faull; James M Olson; Lesley Jones; Ruth Luthi-Carter Journal: Hum Mol Genet Date: 2006-02-08 Impact factor: 6.150
Authors: C Zuccato; A Ciammola; D Rigamonti; B R Leavitt; D Goffredo; L Conti; M E MacDonald; R M Friedlander; V Silani; M R Hayden; T Timmusk; S Sipione; E Cattaneo Journal: Science Date: 2001-06-14 Impact factor: 47.728