{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/108231"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/108231","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Role of microRNA-host-lncRNAs in cell cycle","abstract":"Made available in DSpace on 2020-08-27T00:46:52Z (GMT). No. of bitstreams: 2 SUN-DISSERTATION-2020.pdf: 9175277 bytes, checksum: e2efccee2ecdb753df410d65867ed198 (MD5) LICENSE.txt: 4206 bytes, checksum: d9400be8634f345516a8365c493c941a (MD5) Previous issue date: 2020-03-17","abstract_html":"Made available in DSpace on 2020-08-27T00:46:52Z (GMT). No. of bitstreams: 2 SUN-DISSERTATION-2020.pdf: 9175277 bytes, checksum: e2efccee2ecdb753df410d65867ed198 (MD5) LICENSE.txt: 4206 bytes, checksum: d9400be8634f345516a8365c493c941a (MD5) Previous issue date: 2020-03-17","abstract_has_math":false,"creators":["Sun, Qinyu"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Cell and Developmental Biology","degree_department":null,"school":null,"contributors":["Prasanth, Kannanganattu V","Chen, Jie","Ceman, Stephanie","Kalsotra, Auinash"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2020,"date_issued":"2020-08-27T00:46:52Z","date_published":"2020-08-27T00:46:52Z","updated_at":"2026-07-22T22:24:48Z","subjects":["lncRNA, cell cycle, microRNA-host-gene"],"languages":["en"],"rights":["Copyright 2020 Qinyu Sun"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/108231","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Prasanth, Kannanganattu V","Chen, Jie","Ceman, Stephanie","Kalsotra, Auinash"]},{"key":"dc:creator","label":"Author","values":["Sun, Qinyu"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2020-08-27T00:46:52Z","2022-08-27T00:51:40Z","2020-03-17","2020-05"]},{"key":"dc:type","label":"Dc Type","values":["text","Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Cell and Developmental Biology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["lncRNA, cell cycle, microRNA-host-gene"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2020 Qinyu Sun"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/108231"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Made available in DSpace on 2020-08-27T00:46:52Z (GMT). No. of bitstreams: 2 SUN-DISSERTATION-2020.pdf: 9175277 bytes, checksum: e2efccee2ecdb753df410d65867ed198 (MD5) LICENSE.txt: 4206 bytes, checksum: d9400be8634f345516a8365c493c941a (MD5) Previous issue date: 2020-03-17","Embargo set by: Seth Robbins for item 115844 Lift date: 2022-08-27T00:46:59Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Embargo set by: Seth Robbins for item 115844 Lift date: 2022-08-27T00:50:22Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Embargo set by: Seth Robbins for item 115844 Lift date: 2022-08-27T00:51:40Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Long non-coding RNAs (lncRNAs) regulate vital biological processes, including cell proliferation, differentiation and development. A subclass of lncRNAs is synthesized from microRNA (miRNA) host genes (MIRHGs) due to pre-miRNA processing and are categorized as microRNA-host gene lncRNAs (lnc-MIRHGs). Presently, the cellular function of most lnc-MIRHGs is not well understood. In this thesis, I describe studies showing the potential role of two lnc-MIRHGs in cell cycle progression. In chapter 2, I focus on investigating the role of lnc-MIRHGs in regulating the cell cycle re-entry post quiescence. Cellular quiescence is coupled with cellular development, tissue homeostasis, and cancer progression. Both quiescence and cell cycle re-entry are controlled by active and precise regulation of gene expression. However, the roles of long noncoding RNAs (lncRNAs) during these processes remain to be elucidated. By performing a genome-wide transcriptome analysis, I identify thousands of differentially expressed lncRNAs, including ~30 lnc-MIRHGs, during cellular quiescence and during serum-stimulation in human diploid fibroblast cells. I observe that the mature MIR222HG display serum-stimulated induction due to enhanced pre-RNA splicing. Serum-stimulated binding of the pre-mRNA splicing factor SRSF1 to a micro-exon, which partially overlaps with the primary miR-222 precursor, facilitates enhanced MIR222HG splicing. In serum-stimulated cells, SRSF1 negatively regulates the Drosha/DGCR8-catalyzed cleavage of pri-miR-222, thereby increasing the cellular pool of the mature MIR222HG. Further, loss-of-function studies indicate that the mature MIR222HG facilitates the serum-stimulated cell cycle re-entry in a microRNA-independent manner. Mechanistically, MIR222HG, along with ILF3/2 complex, forms a RNA:RNA duplex with DNM3OS lncRNA, thereby promoting DNM3OS stability. This study identifies a mechanism in which the interplay between splicing versus microprocessor complex dictates the serum-induced expression of MIR222HG for efficient cell cycle re-entry. In Chapter 3, I demonstrate a microRNA-independent role for a nuclear-enriched and G1-elevated lnc-MIRHG in cell cycle progression of human osteosarcoma. Our knowledge of protein-coding genes in cell cycle regulation is rather complete, but the roles of lncRNAs in this important biological process remain to be elucidated. By performing the genome-wide transcriptome profiling analysis, I discovered 38 phase-specific lnc-MIRHGs that showed elevated expression in one particular cell cycle stage (G1, G1S, S, G2, or M). I further show that MIR100HG produces spliced and stable lncRNAs that display elevated levels during the G1 phase of the cell cycle. Depletion of MIR100HG-encoded lncRNAs in human cells results in aberrant cell cycle progression without altering the levels of miRNA encoded within MIR100HG. Notably, MIR100HG interacts with HuR/ELAVL1 as well as with several HuR-target mRNAs. Further, MIR100HG-depleted cells show reduced interaction between HuR and three of its target mRNAs, indicating that MIR100HG facilitates interaction between HuR and target mRNAs. This study unearths novel roles played by a MIRHG-encoded lncRNA in regulating RNA binding protein activity. In Chapter 4, I summarize my findings during the discovery of lnc-MIRHGs and discuss my opinions about the future directions of lnc-MIRHGs research.","Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2022-05-01","The student, Qinyu Sun, accepted the attached license on 2020-03-12 at 20:35.","The student, Qinyu Sun, submitted this Dissertation for approval on 2020-03-12 at 20:36.","This Dissertation was approved for publication on 2020-03-17 at 08:31.","DSpace SAF Submission Ingestion Package generated from Vireo submission #14895 on 2020-08-25 at 17:39:01","Author requested closed access (OA after 2yrs) in Vireo ETD system","Limited"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Role of microRNA-host-lncRNAs in cell cycle"]}]}],"canonical_facts":{"dc:contributor":["Prasanth, Kannanganattu V","Chen, Jie","Ceman, Stephanie","Kalsotra, Auinash"],"dc:creator":["Sun, Qinyu"],"dc:date":["2020-08-27T00:46:52Z","2022-08-27T00:51:40Z","2020-03-17","2020-05"],"dc:description":["Made available in DSpace on 2020-08-27T00:46:52Z (GMT). No. of bitstreams: 2 SUN-DISSERTATION-2020.pdf: 9175277 bytes, checksum: e2efccee2ecdb753df410d65867ed198 (MD5) LICENSE.txt: 4206 bytes, checksum: d9400be8634f345516a8365c493c941a (MD5) Previous issue date: 2020-03-17","Embargo set by: Seth Robbins for item 115844 Lift date: 2022-08-27T00:46:59Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Embargo set by: Seth Robbins for item 115844 Lift date: 2022-08-27T00:50:22Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Embargo set by: Seth Robbins for item 115844 Lift date: 2022-08-27T00:51:40Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Long non-coding RNAs (lncRNAs) regulate vital biological processes, including cell proliferation, differentiation and development. A subclass of lncRNAs is synthesized from microRNA (miRNA) host genes (MIRHGs) due to pre-miRNA processing and are categorized as microRNA-host gene lncRNAs (lnc-MIRHGs). Presently, the cellular function of most lnc-MIRHGs is not well understood. In this thesis, I describe studies showing the potential role of two lnc-MIRHGs in cell cycle progression. In chapter 2, I focus on investigating the role of lnc-MIRHGs in regulating the cell cycle re-entry post quiescence. Cellular quiescence is coupled with cellular development, tissue homeostasis, and cancer progression. Both quiescence and cell cycle re-entry are controlled by active and precise regulation of gene expression. However, the roles of long noncoding RNAs (lncRNAs) during these processes remain to be elucidated. By performing a genome-wide transcriptome analysis, I identify thousands of differentially expressed lncRNAs, including ~30 lnc-MIRHGs, during cellular quiescence and during serum-stimulation in human diploid fibroblast cells. I observe that the mature MIR222HG display serum-stimulated induction due to enhanced pre-RNA splicing. Serum-stimulated binding of the pre-mRNA splicing factor SRSF1 to a micro-exon, which partially overlaps with the primary miR-222 precursor, facilitates enhanced MIR222HG splicing. In serum-stimulated cells, SRSF1 negatively regulates the Drosha/DGCR8-catalyzed cleavage of pri-miR-222, thereby increasing the cellular pool of the mature MIR222HG. Further, loss-of-function studies indicate that the mature MIR222HG facilitates the serum-stimulated cell cycle re-entry in a microRNA-independent manner. Mechanistically, MIR222HG, along with ILF3/2 complex, forms a RNA:RNA duplex with DNM3OS lncRNA, thereby promoting DNM3OS stability. This study identifies a mechanism in which the interplay between splicing versus microprocessor complex dictates the serum-induced expression of MIR222HG for efficient cell cycle re-entry. In Chapter 3, I demonstrate a microRNA-independent role for a nuclear-enriched and G1-elevated lnc-MIRHG in cell cycle progression of human osteosarcoma. Our knowledge of protein-coding genes in cell cycle regulation is rather complete, but the roles of lncRNAs in this important biological process remain to be elucidated. By performing the genome-wide transcriptome profiling analysis, I discovered 38 phase-specific lnc-MIRHGs that showed elevated expression in one particular cell cycle stage (G1, G1S, S, G2, or M). I further show that MIR100HG produces spliced and stable lncRNAs that display elevated levels during the G1 phase of the cell cycle. Depletion of MIR100HG-encoded lncRNAs in human cells results in aberrant cell cycle progression without altering the levels of miRNA encoded within MIR100HG. Notably, MIR100HG interacts with HuR/ELAVL1 as well as with several HuR-target mRNAs. Further, MIR100HG-depleted cells show reduced interaction between HuR and three of its target mRNAs, indicating that MIR100HG facilitates interaction between HuR and target mRNAs. This study unearths novel roles played by a MIRHG-encoded lncRNA in regulating RNA binding protein activity. In Chapter 4, I summarize my findings during the discovery of lnc-MIRHGs and discuss my opinions about the future directions of lnc-MIRHGs research.","Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2022-05-01","The student, Qinyu Sun, accepted the attached license on 2020-03-12 at 20:35.","The student, Qinyu Sun, submitted this Dissertation for approval on 2020-03-12 at 20:36.","This Dissertation was approved for publication on 2020-03-17 at 08:31.","DSpace SAF Submission Ingestion Package generated from Vireo submission #14895 on 2020-08-25 at 17:39:01","Author requested closed access (OA after 2yrs) in Vireo ETD system","Limited"],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/2142/108231"],"dc:language":["en"],"dc:rights":["Copyright 2020 Qinyu Sun"],"dc:subject":["lncRNA, cell cycle, microRNA-host-gene"],"dc:title":["Role of microRNA-host-lncRNAs in cell cycle"],"dc:type":["text","Thesis"],"thesis:degree_discipline":["Cell and Developmental Biology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:24:48Z"}