{"id":{"repo_id":"ohiolink","oai_identifier":"oai:etd.ohiolink.edu:osu1366055621"},"canonical_url":"https://search.dev.ndltd.org/etd/ohiolink/oai:etd.ohiolink.edu:osu1366055621","repository":{"repo_id":"ohiolink","name":"OhioLINK","base_url":"https://etd.ohiolink.edu/acprod/odb_etd/ws/oai/oai"},"display":{"title":"MiR-128 controls the activity of Polycomb Repressor Complexes 1 and 2 in Neural Stem Cells: Implications of its loss in gliomagenesis.","abstract":"The Polycomb Repressor Complex (PRC) is an epigenetic regulator of transcription whose action is mediated by two protein complexes, PRC1 and PRC2. PRC activity normally plays a key role in stem cell maintenance, but it is oncogenic in glioblastoma where it is involved in cancer stem cell maintenance and radio-resistance. Here we show that miR-128 directly targets the mRNA of BMI1 and SUZ12, key components of PRC1 and PRC2, respectively. This blocks the partially redundant functions of PRC1/PRC2, thereby significantly reducing PRC activity and its associated histone modifications. MiR-128 and SUZ12/BMI1 show opposite expression in human glioblastomas versus normal brain and in glioma stem-like versus neural stem cells. MiR-128 expression is significantly reduced in the brain of young mice genetically engineered to develop glioblastomas before tumor development, as compared to the elevated expression of miR-128 in the brain of wild-type mice. This suggests that loss of miR-128 expression in brain is an early event in gliomagenesis. Moreover, knock-down of miR-128 expression in non-malignant mouse and human neural stem cells led to elevated expression of PRC components and increased clonogenicity, suggesting that miR-128 is an important suppressor of PRC activity and its absence is an early event in gliomagenesis. Finally, miR-128 renders glioma initiating cells less radio-resistant by preventing the radiation-induced expression of both PRC components thus impairing the DNA repair after radiation-induced double strand DNA breaks.Taken together our results suggest an important role for the loss of miR-128 in the pathogenesis of glioblastoma and its potential for a future therapeutic use.","abstract_html":"The Polycomb Repressor Complex (PRC) is an epigenetic regulator of transcription whose action is mediated by two protein complexes, PRC1 and PRC2. PRC activity normally plays a key role in stem cell maintenance, but it is oncogenic in glioblastoma where it is involved in cancer stem cell maintenance and radio-resistance. Here we show that miR-128 directly targets the mRNA of BMI1 and SUZ12, key components of PRC1 and PRC2, respectively. This blocks the partially redundant functions of PRC1/PRC2, thereby significantly reducing PRC activity and its associated histone modifications. MiR-128 and SUZ12/BMI1 show opposite expression in human glioblastomas versus normal brain and in glioma stem-like versus neural stem cells. MiR-128 expression is significantly reduced in the brain of young mice genetically engineered to develop glioblastomas before tumor development, as compared to the elevated expression of miR-128 in the brain of wild-type mice. This suggests that loss of miR-128 expression in brain is an early event in gliomagenesis. Moreover, knock-down of miR-128 expression in non-malignant mouse and human neural stem cells led to elevated expression of PRC components and increased clonogenicity, suggesting that miR-128 is an important suppressor of PRC activity and its absence is an early event in gliomagenesis. Finally, miR-128 renders glioma initiating cells less radio-resistant by preventing the radiation-induced expression of both PRC components thus impairing the DNA repair after radiation-induced double strand DNA breaks.Taken together our results suggest an important role for the loss of miR-128 in the pathogenesis of glioblastoma and its potential for a future therapeutic use.","abstract_has_math":false,"creators":["Peruzzi, Pierpaolo"],"institution":"The Ohio State University","degree_name":"Doctor of Philosophy","degree_level":"doctoral","degree_discipline":"Integrated Biomedical Science Graduate Program","degree_department":null,"school":null,"contributors":["Chiocca, E Antonio"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-08-09","date_published":"2013-08-09","updated_at":"2026-07-24T03:37:46Z","subjects":["Molecular Biology","Oncology","miR-128","glioblastoma","neural stem cells","Polycomb","BMI1","SUZ12"],"languages":["English"],"rights":["unrestricted","This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://rave.ohiolink.edu/etdc/view?acc_num=osu1366055621","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Chiocca, E Antonio"]},{"key":"dc:creator","label":"Author","values":["Peruzzi, Pierpaolo"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2013-08-09"]},{"key":"dc:publisher","label":"Institution","values":["The Ohio State University / OhioLINK"]},{"key":"dc:type","label":"Dc Type","values":["Electronic Thesis or Dissertation"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Integrated Biomedical Science Graduate Program"]},{"key":"thesis:degree_level","label":"Degree Level","values":["doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["The Ohio State University"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Molecular Biology","Oncology","miR-128","glioblastoma","neural stem cells","Polycomb","BMI1","SUZ12"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English"]},{"key":"dc:rights","label":"Dc Rights","values":["unrestricted","This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://rave.ohiolink.edu/etdc/view?acc_num=osu1366055621"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The Polycomb Repressor Complex (PRC) is an epigenetic regulator of transcription whose action is mediated by two protein complexes, PRC1 and PRC2. PRC activity normally plays a key role in stem cell maintenance, but it is oncogenic in glioblastoma where it is involved in cancer stem cell maintenance and radio-resistance. Here we show that miR-128 directly targets the mRNA of BMI1 and SUZ12, key components of PRC1 and PRC2, respectively. This blocks the partially redundant functions of PRC1/PRC2, thereby significantly reducing PRC activity and its associated histone modifications. MiR-128 and SUZ12/BMI1 show opposite expression in human glioblastomas versus normal brain and in glioma stem-like versus neural stem cells. MiR-128 expression is significantly reduced in the brain of young mice genetically engineered to develop glioblastomas before tumor development, as compared to the elevated expression of miR-128 in the brain of wild-type mice. This suggests that loss of miR-128 expression in brain is an early event in gliomagenesis. Moreover, knock-down of miR-128 expression in non-malignant mouse and human neural stem cells led to elevated expression of PRC components and increased clonogenicity, suggesting that miR-128 is an important suppressor of PRC activity and its absence is an early event in gliomagenesis. Finally, miR-128 renders glioma initiating cells less radio-resistant by preventing the radiation-induced expression of both PRC components thus impairing the DNA repair after radiation-induced double strand DNA breaks.Taken together our results suggest an important role for the loss of miR-128 in the pathogenesis of glioblastoma and its potential for a future therapeutic use."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf","3.77 MB"]},{"key":"dc:title","label":"Title","values":["MiR-128 controls the activity of Polycomb Repressor Complexes 1 and 2 in Neural Stem Cells: Implications of its loss in gliomagenesis."]}]}],"canonical_facts":{"dc:contributor":["Chiocca, E Antonio"],"dc:creator":["Peruzzi, Pierpaolo"],"dc:date":["2013-08-09"],"dc:description":["The Polycomb Repressor Complex (PRC) is an epigenetic regulator of transcription whose action is mediated by two protein complexes, PRC1 and PRC2. PRC activity normally plays a key role in stem cell maintenance, but it is oncogenic in glioblastoma where it is involved in cancer stem cell maintenance and radio-resistance. Here we show that miR-128 directly targets the mRNA of BMI1 and SUZ12, key components of PRC1 and PRC2, respectively. This blocks the partially redundant functions of PRC1/PRC2, thereby significantly reducing PRC activity and its associated histone modifications. MiR-128 and SUZ12/BMI1 show opposite expression in human glioblastomas versus normal brain and in glioma stem-like versus neural stem cells. MiR-128 expression is significantly reduced in the brain of young mice genetically engineered to develop glioblastomas before tumor development, as compared to the elevated expression of miR-128 in the brain of wild-type mice. This suggests that loss of miR-128 expression in brain is an early event in gliomagenesis. Moreover, knock-down of miR-128 expression in non-malignant mouse and human neural stem cells led to elevated expression of PRC components and increased clonogenicity, suggesting that miR-128 is an important suppressor of PRC activity and its absence is an early event in gliomagenesis. Finally, miR-128 renders glioma initiating cells less radio-resistant by preventing the radiation-induced expression of both PRC components thus impairing the DNA repair after radiation-induced double strand DNA breaks.Taken together our results suggest an important role for the loss of miR-128 in the pathogenesis of glioblastoma and its potential for a future therapeutic use."],"dc:format":["application/pdf","3.77 MB"],"dc:identifier":["http://rave.ohiolink.edu/etdc/view?acc_num=osu1366055621"],"dc:language":["English"],"dc:publisher":["The Ohio State University / OhioLINK"],"dc:rights":["unrestricted","This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws."],"dc:subject":["Molecular Biology","Oncology","miR-128","glioblastoma","neural stem cells","Polycomb","BMI1","SUZ12"],"dc:title":["MiR-128 controls the activity of Polycomb Repressor Complexes 1 and 2 in Neural Stem Cells: Implications of its loss in gliomagenesis."],"dc:type":["Electronic Thesis or Dissertation"],"thesis:degree_discipline":["Integrated Biomedical Science Graduate Program"],"thesis:degree_level":["doctoral"],"thesis:degree_name":["Doctor of Philosophy"],"thesis:institution_name":["The Ohio State University"]},"updated_at":"2026-07-24T03:37:46Z"}