Altered microRNA expression profile in Amyotrophic Lateral Sclerosis: a role in the regulation of NFL mRNA levels
Amyotrophic Lateral Sclerosis (ALS) is a progressive, adult onset, fatal neurodegenerative disease of motor neurons. There is emerging evidence that alterations in RNA metabolism may be critical in the pathogenesis of ALS. MicroRNAs (miRNAs) are small non-coding RNAs that are key determinants of mRN...
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description | Amyotrophic Lateral Sclerosis (ALS) is a progressive, adult onset, fatal neurodegenerative disease of motor neurons. There is emerging evidence that alterations in RNA metabolism may be critical in the pathogenesis of ALS. MicroRNAs (miRNAs) are small non-coding RNAs that are key determinants of mRNA stability. Considering that miRNAs are increasingly being recognized as having a role in a variety of neurodegenerative diseases, we decided to characterize the miRNA expression profile in spinal cord (SC) tissue in sporadic ALS (sALS) and controls. Furthermore, we performed functional analysis to identify a group of dysregulated miRNAs that could be responsible for the selective suppression of low molecular weight neurofilament (NFL) mRNA observed in ALS.
Using TaqMan arrays we analyzed 664 miRNAs and found that a large number of miRNAs are differentially expressed in ventral lumbar SC in sALS compared to controls. We observed that the majority of dysregulated miRNAs are down-regulated in sALS SC tissues. Ingenuity Pathway Analysis (IPA) showed that dysregulated miRNAs are linked with nervous system function and cell death. We used two prediction algorithms to develop a panel of miRNAs that have recognition elements within the human NFL mRNA 3'UTR, and then we performed functional analysis for these miRNAs. Our results demonstrate that three miRNAs that are dysregulated in sALS (miR-146a*, miR-524-5p and miR-582-3p) are capable of interacting with NFL mRNA 3'UTR in a manner that is consistent with the suppressed steady state mRNA levels observed in spinal motor neurons in ALS.
The miRNA expression profile is broadly altered in the SC in sALS. Amongst these is a group of dysregulated miRNAs directly regulate the NFL mRNA 3'UTR, suggesting a role in the selective suppression of NFL mRNA in the ALS spinal motor neuron neurofilamentous aggregate formation. |
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Using TaqMan arrays we analyzed 664 miRNAs and found that a large number of miRNAs are differentially expressed in ventral lumbar SC in sALS compared to controls. We observed that the majority of dysregulated miRNAs are down-regulated in sALS SC tissues. Ingenuity Pathway Analysis (IPA) showed that dysregulated miRNAs are linked with nervous system function and cell death. We used two prediction algorithms to develop a panel of miRNAs that have recognition elements within the human NFL mRNA 3'UTR, and then we performed functional analysis for these miRNAs. Our results demonstrate that three miRNAs that are dysregulated in sALS (miR-146a*, miR-524-5p and miR-582-3p) are capable of interacting with NFL mRNA 3'UTR in a manner that is consistent with the suppressed steady state mRNA levels observed in spinal motor neurons in ALS.
The miRNA expression profile is broadly altered in the SC in sALS. Amongst these is a group of dysregulated miRNAs directly regulate the NFL mRNA 3'UTR, suggesting a role in the selective suppression of NFL mRNA in the ALS spinal motor neuron neurofilamentous aggregate formation.</description><identifier>ISSN: 1756-6606</identifier><identifier>EISSN: 1756-6606</identifier><identifier>DOI: 10.1186/1756-6606-6-26</identifier><identifier>PMID: 23705811</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>3' Untranslated Regions - genetics ; Adult ; Aged ; Amyotrophic lateral sclerosis ; Amyotrophic Lateral Sclerosis - genetics ; Analysis ; Base Sequence ; Biological products industry ; Case-Control Studies ; Cell death ; Cell Death - genetics ; Demography ; Enzymes ; Female ; Gene Expression Profiling ; Gene Regulatory Networks - genetics ; Genes ; Genes, Reporter - genetics ; HEK293 Cells ; Humans ; Luciferases - metabolism ; Male ; Medical research ; Messenger RNA ; MicroRNA ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Middle Aged ; Molecular Sequence Data ; Mutation ; Mutation - genetics ; Nervous System - pathology ; Nervous System - physiopathology ; Nervous system diseases ; Neurofilament Proteins - genetics ; Neurofilament Proteins - metabolism ; Physiological aspects ; Proteins ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Sequence Alignment ; Spinal Cord - metabolism ; Spinal Cord - pathology ; Up-Regulation - genetics</subject><ispartof>Molecular brain, 2013-05, Vol.6 (1), p.26-26, Article 26</ispartof><rights>COPYRIGHT 2013 BioMed Central Ltd.</rights><rights>2013 Campos-Melo et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><rights>Copyright © 2013 Campos-Melo et al.; licensee BioMed Central Ltd. 2013 Campos-Melo et al.; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b642t-95804b05c2652b31ade3d91b7dc4489cc7d7ae70007e7f624473681d6e763eb73</citedby><cites>FETCH-LOGICAL-b642t-95804b05c2652b31ade3d91b7dc4489cc7d7ae70007e7f624473681d6e763eb73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3668997/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3668997/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23705811$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Campos-Melo, Danae</creatorcontrib><creatorcontrib>Droppelmann, Cristian A</creatorcontrib><creatorcontrib>He, Zhongping</creatorcontrib><creatorcontrib>Volkening, Kathryn</creatorcontrib><creatorcontrib>Strong, Michael J</creatorcontrib><title>Altered microRNA expression profile in Amyotrophic Lateral Sclerosis: a role in the regulation of NFL mRNA levels</title><title>Molecular brain</title><addtitle>Mol Brain</addtitle><description>Amyotrophic Lateral Sclerosis (ALS) is a progressive, adult onset, fatal neurodegenerative disease of motor neurons. There is emerging evidence that alterations in RNA metabolism may be critical in the pathogenesis of ALS. MicroRNAs (miRNAs) are small non-coding RNAs that are key determinants of mRNA stability. Considering that miRNAs are increasingly being recognized as having a role in a variety of neurodegenerative diseases, we decided to characterize the miRNA expression profile in spinal cord (SC) tissue in sporadic ALS (sALS) and controls. Furthermore, we performed functional analysis to identify a group of dysregulated miRNAs that could be responsible for the selective suppression of low molecular weight neurofilament (NFL) mRNA observed in ALS.
Using TaqMan arrays we analyzed 664 miRNAs and found that a large number of miRNAs are differentially expressed in ventral lumbar SC in sALS compared to controls. We observed that the majority of dysregulated miRNAs are down-regulated in sALS SC tissues. Ingenuity Pathway Analysis (IPA) showed that dysregulated miRNAs are linked with nervous system function and cell death. We used two prediction algorithms to develop a panel of miRNAs that have recognition elements within the human NFL mRNA 3'UTR, and then we performed functional analysis for these miRNAs. Our results demonstrate that three miRNAs that are dysregulated in sALS (miR-146a*, miR-524-5p and miR-582-3p) are capable of interacting with NFL mRNA 3'UTR in a manner that is consistent with the suppressed steady state mRNA levels observed in spinal motor neurons in ALS.
The miRNA expression profile is broadly altered in the SC in sALS. Amongst these is a group of dysregulated miRNAs directly regulate the NFL mRNA 3'UTR, suggesting a role in the selective suppression of NFL mRNA in the ALS spinal motor neuron neurofilamentous aggregate formation.</description><subject>3' Untranslated Regions - genetics</subject><subject>Adult</subject><subject>Aged</subject><subject>Amyotrophic lateral sclerosis</subject><subject>Amyotrophic Lateral Sclerosis - genetics</subject><subject>Analysis</subject><subject>Base Sequence</subject><subject>Biological products industry</subject><subject>Case-Control Studies</subject><subject>Cell death</subject><subject>Cell Death - genetics</subject><subject>Demography</subject><subject>Enzymes</subject><subject>Female</subject><subject>Gene Expression Profiling</subject><subject>Gene Regulatory Networks - genetics</subject><subject>Genes</subject><subject>Genes, Reporter - genetics</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Luciferases - metabolism</subject><subject>Male</subject><subject>Medical research</subject><subject>Messenger RNA</subject><subject>MicroRNA</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Middle Aged</subject><subject>Molecular Sequence Data</subject><subject>Mutation</subject><subject>Mutation - genetics</subject><subject>Nervous System - pathology</subject><subject>Nervous System - physiopathology</subject><subject>Nervous system diseases</subject><subject>Neurofilament Proteins - genetics</subject><subject>Neurofilament Proteins - metabolism</subject><subject>Physiological aspects</subject><subject>Proteins</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Sequence Alignment</subject><subject>Spinal Cord - metabolism</subject><subject>Spinal Cord - pathology</subject><subject>Up-Regulation - genetics</subject><issn>1756-6606</issn><issn>1756-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNks1r3DAQxU1paNK01x6LoJdenEqWPbJ7KJjQfMCSQj_OQpbHuwqy5Uh2aP77yt1km6QpFIEkpN88hjcvSd4wesRYCR-YKCAFoHFLM3iWHOwent-77ycvQ7ikFDJgxYtkP-OCFiVjB8lVbSf02JLeaO--XtQEf44eQzBuIKN3nbFIzEDq_sZN3o0bo8lKxRJlyTdt0btgwkeiiHdbcNog8bierZoWCdeRi5MV6Rdli9dow6tkr1M24Ovb8zD5cfL5-_FZuvpyen5cr9IG8mxKq6KkeUMLnUGRNZypFnlbsUa0Os_LSmvRCoWCUipQdJDlueBQshZQAMdG8MPk01Z3nJseW43DFJuWoze98jfSKSMf_gxmI9fuWnKAsqoWgXor0Bj3D4GHP9r1crFcLpZLkBlEjfe3TXh3NWOYZG-CRmvVgG4OknGR0TgTyv4DhVwwWkAZ0XeP0Es3-yG6-ZsqS8EK9odaK4vSDF0coNKLqKwLnguomKCROnqCiqvFGAk34JKAJwtiXkLw2O0cYVQumfzbg7f3B7HD70LIfwGy5trO</recordid><startdate>20130524</startdate><enddate>20130524</enddate><creator>Campos-Melo, Danae</creator><creator>Droppelmann, Cristian A</creator><creator>He, Zhongping</creator><creator>Volkening, Kathryn</creator><creator>Strong, Michael J</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7TM</scope><scope>5PM</scope></search><sort><creationdate>20130524</creationdate><title>Altered microRNA expression profile in Amyotrophic Lateral Sclerosis: a role in the regulation of NFL mRNA levels</title><author>Campos-Melo, Danae ; Droppelmann, Cristian A ; He, Zhongping ; Volkening, Kathryn ; Strong, Michael J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b642t-95804b05c2652b31ade3d91b7dc4489cc7d7ae70007e7f624473681d6e763eb73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>3' Untranslated Regions - genetics</topic><topic>Adult</topic><topic>Aged</topic><topic>Amyotrophic lateral sclerosis</topic><topic>Amyotrophic Lateral Sclerosis - genetics</topic><topic>Analysis</topic><topic>Base Sequence</topic><topic>Biological products industry</topic><topic>Case-Control Studies</topic><topic>Cell death</topic><topic>Cell Death - genetics</topic><topic>Demography</topic><topic>Enzymes</topic><topic>Female</topic><topic>Gene Expression Profiling</topic><topic>Gene Regulatory Networks - genetics</topic><topic>Genes</topic><topic>Genes, Reporter - genetics</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Luciferases - metabolism</topic><topic>Male</topic><topic>Medical research</topic><topic>Messenger RNA</topic><topic>MicroRNA</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Middle Aged</topic><topic>Molecular Sequence Data</topic><topic>Mutation</topic><topic>Mutation - genetics</topic><topic>Nervous System - pathology</topic><topic>Nervous System - physiopathology</topic><topic>Nervous system diseases</topic><topic>Neurofilament Proteins - genetics</topic><topic>Neurofilament Proteins - metabolism</topic><topic>Physiological aspects</topic><topic>Proteins</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Sequence Alignment</topic><topic>Spinal Cord - metabolism</topic><topic>Spinal Cord - pathology</topic><topic>Up-Regulation - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Campos-Melo, Danae</creatorcontrib><creatorcontrib>Droppelmann, Cristian A</creatorcontrib><creatorcontrib>He, Zhongping</creatorcontrib><creatorcontrib>Volkening, Kathryn</creatorcontrib><creatorcontrib>Strong, Michael J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>Nucleic Acids Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular brain</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Campos-Melo, Danae</au><au>Droppelmann, Cristian A</au><au>He, Zhongping</au><au>Volkening, Kathryn</au><au>Strong, Michael J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Altered microRNA expression profile in Amyotrophic Lateral Sclerosis: a role in the regulation of NFL mRNA levels</atitle><jtitle>Molecular brain</jtitle><addtitle>Mol Brain</addtitle><date>2013-05-24</date><risdate>2013</risdate><volume>6</volume><issue>1</issue><spage>26</spage><epage>26</epage><pages>26-26</pages><artnum>26</artnum><issn>1756-6606</issn><eissn>1756-6606</eissn><abstract>Amyotrophic Lateral Sclerosis (ALS) is a progressive, adult onset, fatal neurodegenerative disease of motor neurons. There is emerging evidence that alterations in RNA metabolism may be critical in the pathogenesis of ALS. MicroRNAs (miRNAs) are small non-coding RNAs that are key determinants of mRNA stability. Considering that miRNAs are increasingly being recognized as having a role in a variety of neurodegenerative diseases, we decided to characterize the miRNA expression profile in spinal cord (SC) tissue in sporadic ALS (sALS) and controls. Furthermore, we performed functional analysis to identify a group of dysregulated miRNAs that could be responsible for the selective suppression of low molecular weight neurofilament (NFL) mRNA observed in ALS.
Using TaqMan arrays we analyzed 664 miRNAs and found that a large number of miRNAs are differentially expressed in ventral lumbar SC in sALS compared to controls. We observed that the majority of dysregulated miRNAs are down-regulated in sALS SC tissues. Ingenuity Pathway Analysis (IPA) showed that dysregulated miRNAs are linked with nervous system function and cell death. We used two prediction algorithms to develop a panel of miRNAs that have recognition elements within the human NFL mRNA 3'UTR, and then we performed functional analysis for these miRNAs. Our results demonstrate that three miRNAs that are dysregulated in sALS (miR-146a*, miR-524-5p and miR-582-3p) are capable of interacting with NFL mRNA 3'UTR in a manner that is consistent with the suppressed steady state mRNA levels observed in spinal motor neurons in ALS.
The miRNA expression profile is broadly altered in the SC in sALS. Amongst these is a group of dysregulated miRNAs directly regulate the NFL mRNA 3'UTR, suggesting a role in the selective suppression of NFL mRNA in the ALS spinal motor neuron neurofilamentous aggregate formation.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>23705811</pmid><doi>10.1186/1756-6606-6-26</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | 3' Untranslated Regions - genetics Adult Aged Amyotrophic lateral sclerosis Amyotrophic Lateral Sclerosis - genetics Analysis Base Sequence Biological products industry Case-Control Studies Cell death Cell Death - genetics Demography Enzymes Female Gene Expression Profiling Gene Regulatory Networks - genetics Genes Genes, Reporter - genetics HEK293 Cells Humans Luciferases - metabolism Male Medical research Messenger RNA MicroRNA MicroRNAs - genetics MicroRNAs - metabolism Middle Aged Molecular Sequence Data Mutation Mutation - genetics Nervous System - pathology Nervous System - physiopathology Nervous system diseases Neurofilament Proteins - genetics Neurofilament Proteins - metabolism Physiological aspects Proteins RNA, Messenger - genetics RNA, Messenger - metabolism Sequence Alignment Spinal Cord - metabolism Spinal Cord - pathology Up-Regulation - genetics |
title | Altered microRNA expression profile in Amyotrophic Lateral Sclerosis: a role in the regulation of NFL mRNA levels |
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