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The circular RNA circZFR phosphorylates Rb promoting cervical cancer progression by regulating the SSBP1/CDK2/cyclin E1 complex
As a novel type of non-coding RNA, circular RNAs (circRNAs) play a critical role in the initiation and development of various diseases, including cancer. However, the exact function of circRNAs in human cervical cancer remains largely unknown. We identified the circRNA signature of upregulated circR...
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Published in: | Journal of experimental & clinical cancer research 2021-01, Vol.40 (1), p.48-48, Article 48 |
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description | As a novel type of non-coding RNA, circular RNAs (circRNAs) play a critical role in the initiation and development of various diseases, including cancer. However, the exact function of circRNAs in human cervical cancer remains largely unknown.
We identified the circRNA signature of upregulated circRNAs between cervical cancer and paired adjacent normal tissues. Using two different cohorts and GEO database, a total of six upregulated circRNAs were identified with a fold change > 2, and P |
doi_str_mv | 10.1186/s13046-021-01849-2 |
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We identified the circRNA signature of upregulated circRNAs between cervical cancer and paired adjacent normal tissues. Using two different cohorts and GEO database, a total of six upregulated circRNAs were identified with a fold change > 2, and P < 0.05. Among these six circRNAs, hsa_circ_0072088 (circZFR) was the only exonic circRNA significantly overexpressed in cervical cancer. Functional experiments were performed to investigate the biological function of circZFR. CircRNA pull-down, circRNA immunoprecipitation (circRIP) and Co-immunoprecipitation (Co-IP) assays were executed to investigate the molecular mechanism underlying the function of circZFR.
Functionally, circZFR knockdown represses the proliferation, invasion, and tumor growth. Furthermore, circRNA pull-down experiments combined with mass spectrometry unveil the interactions of circZFR with Single-Stranded DNA Binding Protein 1 (SSBP1). Mechanistically, circZFR bound with SSBP1, thereby promoting the assembly of CDK2/cyclin E1 complexes. The activation of CDK2/cyclin E1 complexes induced p-Rb phosphorylation, thus releasing activated E2F1 leading to cell cycle progression and cell proliferation.
Our findings provide the first evidence that circZFR is a novel onco-circRNA and might be a potential biomarker and therapeutic target for cervical cancer patients.</description><identifier>ISSN: 1756-9966</identifier><identifier>ISSN: 0392-9078</identifier><identifier>EISSN: 1756-9966</identifier><identifier>DOI: 10.1186/s13046-021-01849-2</identifier><identifier>PMID: 33516252</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Antibodies ; Biomarkers ; Cell cycle ; Cell cycle regulation ; Cell growth ; Cervical cancer ; Chemotherapy ; Circular RNAs ; Development and progression ; Gene expression ; Mass spectrometry ; MicroRNAs ; Phosphorylation ; Protein binding ; Proteins ; Radiation therapy ; RNA ; RNA binding protein ; RNA Immunoprecipitation ; Software ; Transcription factors ; Tumors ; Wound healing</subject><ispartof>Journal of experimental & clinical cancer research, 2021-01, Vol.40 (1), p.48-48, Article 48</ispartof><rights>COPYRIGHT 2021 BioMed Central Ltd.</rights><rights>2021. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c594t-db51460a9e5f877b301baf4a25d6d8dd721b18c00aa35f340150963ac65841c83</citedby><cites>FETCH-LOGICAL-c594t-db51460a9e5f877b301baf4a25d6d8dd721b18c00aa35f340150963ac65841c83</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/PMC7846991/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2490936434?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25752,27923,27924,37011,37012,44589,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33516252$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhou, Mingyi</creatorcontrib><creatorcontrib>Yang, Zhuo</creatorcontrib><creatorcontrib>Wang, Danbo</creatorcontrib><creatorcontrib>Chen, Peng</creatorcontrib><creatorcontrib>Zhang, Yong</creatorcontrib><title>The circular RNA circZFR phosphorylates Rb promoting cervical cancer progression by regulating the SSBP1/CDK2/cyclin E1 complex</title><title>Journal of experimental & clinical cancer research</title><addtitle>J Exp Clin Cancer Res</addtitle><description>As a novel type of non-coding RNA, circular RNAs (circRNAs) play a critical role in the initiation and development of various diseases, including cancer. However, the exact function of circRNAs in human cervical cancer remains largely unknown.
We identified the circRNA signature of upregulated circRNAs between cervical cancer and paired adjacent normal tissues. Using two different cohorts and GEO database, a total of six upregulated circRNAs were identified with a fold change > 2, and P < 0.05. Among these six circRNAs, hsa_circ_0072088 (circZFR) was the only exonic circRNA significantly overexpressed in cervical cancer. Functional experiments were performed to investigate the biological function of circZFR. CircRNA pull-down, circRNA immunoprecipitation (circRIP) and Co-immunoprecipitation (Co-IP) assays were executed to investigate the molecular mechanism underlying the function of circZFR.
Functionally, circZFR knockdown represses the proliferation, invasion, and tumor growth. Furthermore, circRNA pull-down experiments combined with mass spectrometry unveil the interactions of circZFR with Single-Stranded DNA Binding Protein 1 (SSBP1). Mechanistically, circZFR bound with SSBP1, thereby promoting the assembly of CDK2/cyclin E1 complexes. The activation of CDK2/cyclin E1 complexes induced p-Rb phosphorylation, thus releasing activated E2F1 leading to cell cycle progression and cell proliferation.
Our findings provide the first evidence that circZFR is a novel onco-circRNA and might be a potential biomarker and therapeutic target for cervical cancer patients.</description><subject>Antibodies</subject><subject>Biomarkers</subject><subject>Cell cycle</subject><subject>Cell cycle regulation</subject><subject>Cell growth</subject><subject>Cervical cancer</subject><subject>Chemotherapy</subject><subject>Circular RNAs</subject><subject>Development and progression</subject><subject>Gene expression</subject><subject>Mass spectrometry</subject><subject>MicroRNAs</subject><subject>Phosphorylation</subject><subject>Protein binding</subject><subject>Proteins</subject><subject>Radiation therapy</subject><subject>RNA</subject><subject>RNA binding protein</subject><subject>RNA Immunoprecipitation</subject><subject>Software</subject><subject>Transcription factors</subject><subject>Tumors</subject><subject>Wound healing</subject><issn>1756-9966</issn><issn>0392-9078</issn><issn>1756-9966</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptkk9v0zAYxiMEYmPwBTigSEiIS1a_ie3YF6RSNpg2AerGhYvlOE7qyok7O5noia-O246tRSiy4j-_57H9-kmS14BOARidBCgQphnKIUPAMM_yJ8kxlIRmnFP6dK9_lLwIYYkQBQ78eXJUFARoTvLj5PfNQqfKeDVa6dP51-l28PN8nq4WLsTm11YOOqTzKl1517nB9G2qtL8zStpUyT72Nyut1yEY16fVOvW6jXZbcoj219cfv8Nk9ukyn6i1sqZPzyBVrltZ_etl8qyRNuhX9_-T5Mf52c3sS3b17fPFbHqVKcLxkNUVAUyR5Jo0rCyrAkElGyxzUtOa1XWZQwVMISRlQZoCIyCI00IqShgGxYqT5GLnWzu5FCtvOunXwkkjthPOt0L6wSirBdFRyIA0iFDMGOIlg6qRumFMNbiuo9eHnddqrDpdK90PXtoD08OV3ixE6-5EyTDlHKLB-3sD725HHQbRmaC0tbLXbgwix_HQFAjdoG__QZdu9H0sVaQ44gXFBX6kWhkvYPrGxX3VxlRMKUEYI85IpE7_Q8Wv1p1RrteNifMHgnd7goWWdlgEZ8chvnM4BPMdqLwLwevmoRiAxCarYpdVEbMqtlkVeRS92S_jg-RvOIs_nv_iSg</recordid><startdate>20210130</startdate><enddate>20210130</enddate><creator>Zhou, Mingyi</creator><creator>Yang, Zhuo</creator><creator>Wang, Danbo</creator><creator>Chen, Peng</creator><creator>Zhang, Yong</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><general>BMC</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20210130</creationdate><title>The circular RNA circZFR phosphorylates Rb promoting cervical cancer progression by regulating the SSBP1/CDK2/cyclin E1 complex</title><author>Zhou, Mingyi ; Yang, Zhuo ; Wang, Danbo ; Chen, Peng ; Zhang, Yong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c594t-db51460a9e5f877b301baf4a25d6d8dd721b18c00aa35f340150963ac65841c83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Antibodies</topic><topic>Biomarkers</topic><topic>Cell cycle</topic><topic>Cell cycle regulation</topic><topic>Cell growth</topic><topic>Cervical cancer</topic><topic>Chemotherapy</topic><topic>Circular RNAs</topic><topic>Development and progression</topic><topic>Gene expression</topic><topic>Mass spectrometry</topic><topic>MicroRNAs</topic><topic>Phosphorylation</topic><topic>Protein binding</topic><topic>Proteins</topic><topic>Radiation therapy</topic><topic>RNA</topic><topic>RNA binding protein</topic><topic>RNA Immunoprecipitation</topic><topic>Software</topic><topic>Transcription factors</topic><topic>Tumors</topic><topic>Wound healing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhou, Mingyi</creatorcontrib><creatorcontrib>Yang, Zhuo</creatorcontrib><creatorcontrib>Wang, Danbo</creatorcontrib><creatorcontrib>Chen, Peng</creatorcontrib><creatorcontrib>Zhang, Yong</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</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 Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Publicly Available Content (ProQuest)</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>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Journal of experimental & clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhou, Mingyi</au><au>Yang, Zhuo</au><au>Wang, Danbo</au><au>Chen, Peng</au><au>Zhang, Yong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The circular RNA circZFR phosphorylates Rb promoting cervical cancer progression by regulating the SSBP1/CDK2/cyclin E1 complex</atitle><jtitle>Journal of experimental & clinical cancer research</jtitle><addtitle>J Exp Clin Cancer Res</addtitle><date>2021-01-30</date><risdate>2021</risdate><volume>40</volume><issue>1</issue><spage>48</spage><epage>48</epage><pages>48-48</pages><artnum>48</artnum><issn>1756-9966</issn><issn>0392-9078</issn><eissn>1756-9966</eissn><abstract>As a novel type of non-coding RNA, circular RNAs (circRNAs) play a critical role in the initiation and development of various diseases, including cancer. However, the exact function of circRNAs in human cervical cancer remains largely unknown.
We identified the circRNA signature of upregulated circRNAs between cervical cancer and paired adjacent normal tissues. Using two different cohorts and GEO database, a total of six upregulated circRNAs were identified with a fold change > 2, and P < 0.05. Among these six circRNAs, hsa_circ_0072088 (circZFR) was the only exonic circRNA significantly overexpressed in cervical cancer. Functional experiments were performed to investigate the biological function of circZFR. CircRNA pull-down, circRNA immunoprecipitation (circRIP) and Co-immunoprecipitation (Co-IP) assays were executed to investigate the molecular mechanism underlying the function of circZFR.
Functionally, circZFR knockdown represses the proliferation, invasion, and tumor growth. Furthermore, circRNA pull-down experiments combined with mass spectrometry unveil the interactions of circZFR with Single-Stranded DNA Binding Protein 1 (SSBP1). Mechanistically, circZFR bound with SSBP1, thereby promoting the assembly of CDK2/cyclin E1 complexes. The activation of CDK2/cyclin E1 complexes induced p-Rb phosphorylation, thus releasing activated E2F1 leading to cell cycle progression and cell proliferation.
Our findings provide the first evidence that circZFR is a novel onco-circRNA and might be a potential biomarker and therapeutic target for cervical cancer patients.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>33516252</pmid><doi>10.1186/s13046-021-01849-2</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Antibodies Biomarkers Cell cycle Cell cycle regulation Cell growth Cervical cancer Chemotherapy Circular RNAs Development and progression Gene expression Mass spectrometry MicroRNAs Phosphorylation Protein binding Proteins Radiation therapy RNA RNA binding protein RNA Immunoprecipitation Software Transcription factors Tumors Wound healing |
title | The circular RNA circZFR phosphorylates Rb promoting cervical cancer progression by regulating the SSBP1/CDK2/cyclin E1 complex |
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