ZKSCAN1 gene and its related circular RNA (circZKSCAN1) both inhibit hepatocellular carcinoma cell growth, migration, and invasion but through different signaling pathways
There is increasing evidence that circular RNA (circRNA) are involved in cancer development, but the regulation and function of human circRNA remain largely unknown. In this study, we demonstrated that ZKSCAN1, a zinc finger family gene, is expressed in both linear and circular (circZKSCAN1) forms o...
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| Veröffentlicht in: | Molecular oncology 2017-04, Vol.11 (4), p.422-437 |
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| creator | Yao, Zhicheng Luo, Jingyan Hu, Kunpeng Lin, Jizong Huang, He Wang, Qiangliang Zhang, Peng Xiong, Zhiyong He, Chonghua Huang, Zejian Liu, Bo Yang, Yang |
| description | There is increasing evidence that circular RNA (circRNA) are involved in cancer development, but the regulation and function of human circRNA remain largely unknown. In this study, we demonstrated that ZKSCAN1, a zinc finger family gene, is expressed in both linear and circular (circZKSCAN1) forms of RNA in human hepatocellular carcinoma (HCC) tissues and cell lines. Here, we analyzed a cohort of 102 patients and found that expression of both ZKSCAN1mRNA and circZKSCAN1 was significantly lower (P |
| doi_str_mv | 10.1002/1878-0261.12045 |
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| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5527481</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A731950720</galeid><sourcerecordid>A731950720</sourcerecordid><originalsourceid>FETCH-LOGICAL-g4875-bdf20c8bdd2d6447a8b5ede33b03a27d4aa90a6f576be2662689175b680911813</originalsourceid><addsrcrecordid>eNptkk2P0zAQhiMEYj_gzA1Z4rJIm2I7sZ1ckKqKBUTZlfi4cLEmsZMYJXZxnK36m_iTOG2pWAn54PHMM6_tmUmSFwQvCMb0DSlEkWLKyYJQnLNHyfnJ8zjaTOSpKEpyllyM40-MGS95-TQ5owUlhBJ2nvz-8enranlLUKutRmAVMmFEXvcQtEK18fXUg0dfbpfoaj4d8deocqFDxnamMgF1egPB1brv93QNvjbWDYBmF2q924buGg2m9RCMs9eHi-w9jPGEqimg0Hk3tR1Spmm01zag0bQWemNbFLW7LezGZ8mTBvpRPz_ul8n3m3ffVh_S9d37j6vlOm3zQrC0Ug3FdVEpRRXPcwFFxbTSWVbhDKhQOUCJgTdM8EpTzimPFRKs4gUuCSlIdpm8PehupmrQqo6v8dDLjTcD-J10YOTDiDWdbN29ZIyKfC9wdRTw7tekxyAHM86lAKvdNEpS8LLksQcioq8OaAu9lsY2LirWMy6XIiMlw4LiSC3-Q8Wl9GBqZ3Vjov9Bwst_v3B6-9_GR4AfgG3M3J3iBMt5ruQ8RXKeIrmfK_n5bk33VvYHdqDAgA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1869968217</pqid></control><display><type>article</type><title>ZKSCAN1 gene and its related circular RNA (circZKSCAN1) both inhibit hepatocellular carcinoma cell growth, migration, and invasion but through different signaling pathways</title><source>MEDLINE</source><source>Wiley Online Library Open Access</source><source>DOAJ Directory of Open Access Journals</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Yao, Zhicheng ; Luo, Jingyan ; Hu, Kunpeng ; Lin, Jizong ; Huang, He ; Wang, Qiangliang ; Zhang, Peng ; Xiong, Zhiyong ; He, Chonghua ; Huang, Zejian ; Liu, Bo ; Yang, Yang</creator><creatorcontrib>Yao, Zhicheng ; Luo, Jingyan ; Hu, Kunpeng ; Lin, Jizong ; Huang, He ; Wang, Qiangliang ; Zhang, Peng ; Xiong, Zhiyong ; He, Chonghua ; Huang, Zejian ; Liu, Bo ; Yang, Yang</creatorcontrib><description>There is increasing evidence that circular RNA (circRNA) are involved in cancer development, but the regulation and function of human circRNA remain largely unknown. In this study, we demonstrated that ZKSCAN1, a zinc finger family gene, is expressed in both linear and circular (circZKSCAN1) forms of RNA in human hepatocellular carcinoma (HCC) tissues and cell lines. Here, we analyzed a cohort of 102 patients and found that expression of both ZKSCAN1mRNA and circZKSCAN1 was significantly lower (P < 0.05) in the HCC samples compared with that in matched adjacent nontumorous tissues by reverse transcription PCR (RT‐PCR). The low expression level of ZKSCAN1 was only associated with tumor size (P = 0.032), while the cirZKSCAN1 levels varied in patients with different tumor numbers (P < 0.01), cirrhosis (P = 0.031), vascular invasion (P = 0.002), or microscopic vascular invasion (P = 0.002), as well as with the tumor grade (P < 0.001). Silencing both ZKSCAN1mRNA and circZKSCAN1 promoted cell proliferation, migration, and invasion. In contrast, overexpression of both forms of RNA repressed HCC progression in vivo and in vitro. Silencing or overexpression of both forms of RNA did not interfere with each other. RNA‐seq revealed a very different molecular basis for the observed effects; ZKSCAN1mRNA mainly regulated cellular metabolism, while circZKSCAN1 mediated several cancer‐related signaling pathways, suggesting a nonredundant role for ZKSCAN1mRNA and circRNA. In conclusion, our results revealed two post‐translational products (ZKSCAN1mRNA and circZKSCAN1) that cooperated closely with one another to inhibit growth, migration, and invasion of HCC. cirZKSCAN1 might be a useful marker for the diagnosis of HCC.
Circular RNA have recently been shown to play a regulatory role in disease. We investigated the role of circRNA transcribed from ZKSCAN1, a member of the zinc finger family. Our results revealed two post‐translational products (ZKSCAN1 mRNA and circZKSCAN1) that cooperated closely with one another to inhibit cancer growth migration and invasion, but which affected different signaling pathways.</description><identifier>ISSN: 1574-7891</identifier><identifier>EISSN: 1878-0261</identifier><identifier>DOI: 10.1002/1878-0261.12045</identifier><identifier>PMID: 28211215</identifier><language>eng</language><publisher>United States: John Wiley & Sons, Inc</publisher><subject>Animals ; Base Sequence ; Cancer ; Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - pathology ; Cell Line, Tumor ; Cell Movement - genetics ; Cell Proliferation - genetics ; circular RNA ; Demography ; Down-Regulation - genetics ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genes ; Genetic aspects ; Genetic research ; Growth ; HCC ; Hepatoma ; Humans ; Liver Neoplasms - genetics ; Liver Neoplasms - pathology ; Male ; Mice, Nude ; Middle Aged ; Neoplasm Invasiveness ; Physiological aspects ; qRT‐PCR ; Reproducibility of Results ; RNA ; RNA - genetics ; RNA - metabolism ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; RNA‐seq ; ROC Curve ; Sequence Analysis, RNA ; Signal Transduction - genetics ; Transcription Factors - genetics ; Transcription Factors - metabolism ; ZKSCAN1</subject><ispartof>Molecular oncology, 2017-04, Vol.11 (4), p.422-437</ispartof><rights>2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.</rights><rights>COPYRIGHT 2017 John Wiley & Sons, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5527481/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5527481/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28211215$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yao, Zhicheng</creatorcontrib><creatorcontrib>Luo, Jingyan</creatorcontrib><creatorcontrib>Hu, Kunpeng</creatorcontrib><creatorcontrib>Lin, Jizong</creatorcontrib><creatorcontrib>Huang, He</creatorcontrib><creatorcontrib>Wang, Qiangliang</creatorcontrib><creatorcontrib>Zhang, Peng</creatorcontrib><creatorcontrib>Xiong, Zhiyong</creatorcontrib><creatorcontrib>He, Chonghua</creatorcontrib><creatorcontrib>Huang, Zejian</creatorcontrib><creatorcontrib>Liu, Bo</creatorcontrib><creatorcontrib>Yang, Yang</creatorcontrib><title>ZKSCAN1 gene and its related circular RNA (circZKSCAN1) both inhibit hepatocellular carcinoma cell growth, migration, and invasion but through different signaling pathways</title><title>Molecular oncology</title><addtitle>Mol Oncol</addtitle><description>There is increasing evidence that circular RNA (circRNA) are involved in cancer development, but the regulation and function of human circRNA remain largely unknown. In this study, we demonstrated that ZKSCAN1, a zinc finger family gene, is expressed in both linear and circular (circZKSCAN1) forms of RNA in human hepatocellular carcinoma (HCC) tissues and cell lines. Here, we analyzed a cohort of 102 patients and found that expression of both ZKSCAN1mRNA and circZKSCAN1 was significantly lower (P < 0.05) in the HCC samples compared with that in matched adjacent nontumorous tissues by reverse transcription PCR (RT‐PCR). The low expression level of ZKSCAN1 was only associated with tumor size (P = 0.032), while the cirZKSCAN1 levels varied in patients with different tumor numbers (P < 0.01), cirrhosis (P = 0.031), vascular invasion (P = 0.002), or microscopic vascular invasion (P = 0.002), as well as with the tumor grade (P < 0.001). Silencing both ZKSCAN1mRNA and circZKSCAN1 promoted cell proliferation, migration, and invasion. In contrast, overexpression of both forms of RNA repressed HCC progression in vivo and in vitro. Silencing or overexpression of both forms of RNA did not interfere with each other. RNA‐seq revealed a very different molecular basis for the observed effects; ZKSCAN1mRNA mainly regulated cellular metabolism, while circZKSCAN1 mediated several cancer‐related signaling pathways, suggesting a nonredundant role for ZKSCAN1mRNA and circRNA. In conclusion, our results revealed two post‐translational products (ZKSCAN1mRNA and circZKSCAN1) that cooperated closely with one another to inhibit growth, migration, and invasion of HCC. cirZKSCAN1 might be a useful marker for the diagnosis of HCC.
Circular RNA have recently been shown to play a regulatory role in disease. We investigated the role of circRNA transcribed from ZKSCAN1, a member of the zinc finger family. Our results revealed two post‐translational products (ZKSCAN1 mRNA and circZKSCAN1) that cooperated closely with one another to inhibit cancer growth migration and invasion, but which affected different signaling pathways.</description><subject>Animals</subject><subject>Base Sequence</subject><subject>Cancer</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - genetics</subject><subject>Cell Proliferation - genetics</subject><subject>circular RNA</subject><subject>Demography</subject><subject>Down-Regulation - genetics</subject><subject>Female</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic research</subject><subject>Growth</subject><subject>HCC</subject><subject>Hepatoma</subject><subject>Humans</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - pathology</subject><subject>Male</subject><subject>Mice, Nude</subject><subject>Middle Aged</subject><subject>Neoplasm Invasiveness</subject><subject>Physiological aspects</subject><subject>qRT‐PCR</subject><subject>Reproducibility of Results</subject><subject>RNA</subject><subject>RNA - genetics</subject><subject>RNA - metabolism</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>RNA‐seq</subject><subject>ROC Curve</subject><subject>Sequence Analysis, RNA</subject><subject>Signal Transduction - genetics</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>ZKSCAN1</subject><issn>1574-7891</issn><issn>1878-0261</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNptkk2P0zAQhiMEYj_gzA1Z4rJIm2I7sZ1ckKqKBUTZlfi4cLEmsZMYJXZxnK36m_iTOG2pWAn54PHMM6_tmUmSFwQvCMb0DSlEkWLKyYJQnLNHyfnJ8zjaTOSpKEpyllyM40-MGS95-TQ5owUlhBJ2nvz-8enranlLUKutRmAVMmFEXvcQtEK18fXUg0dfbpfoaj4d8deocqFDxnamMgF1egPB1brv93QNvjbWDYBmF2q924buGg2m9RCMs9eHi-w9jPGEqimg0Hk3tR1Spmm01zag0bQWemNbFLW7LezGZ8mTBvpRPz_ul8n3m3ffVh_S9d37j6vlOm3zQrC0Ug3FdVEpRRXPcwFFxbTSWVbhDKhQOUCJgTdM8EpTzimPFRKs4gUuCSlIdpm8PehupmrQqo6v8dDLjTcD-J10YOTDiDWdbN29ZIyKfC9wdRTw7tekxyAHM86lAKvdNEpS8LLksQcioq8OaAu9lsY2LirWMy6XIiMlw4LiSC3-Q8Wl9GBqZ3Vjov9Bwst_v3B6-9_GR4AfgG3M3J3iBMt5ruQ8RXKeIrmfK_n5bk33VvYHdqDAgA</recordid><startdate>201704</startdate><enddate>201704</enddate><creator>Yao, Zhicheng</creator><creator>Luo, Jingyan</creator><creator>Hu, Kunpeng</creator><creator>Lin, Jizong</creator><creator>Huang, He</creator><creator>Wang, Qiangliang</creator><creator>Zhang, Peng</creator><creator>Xiong, Zhiyong</creator><creator>He, Chonghua</creator><creator>Huang, Zejian</creator><creator>Liu, Bo</creator><creator>Yang, Yang</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201704</creationdate><title>ZKSCAN1 gene and its related circular RNA (circZKSCAN1) both inhibit hepatocellular carcinoma cell growth, migration, and invasion but through different signaling pathways</title><author>Yao, Zhicheng ; Luo, Jingyan ; Hu, Kunpeng ; Lin, Jizong ; Huang, He ; Wang, Qiangliang ; Zhang, Peng ; Xiong, Zhiyong ; He, Chonghua ; Huang, Zejian ; Liu, Bo ; Yang, Yang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-g4875-bdf20c8bdd2d6447a8b5ede33b03a27d4aa90a6f576be2662689175b680911813</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Base Sequence</topic><topic>Cancer</topic><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - genetics</topic><topic>Cell Proliferation - genetics</topic><topic>circular RNA</topic><topic>Demography</topic><topic>Down-Regulation - genetics</topic><topic>Female</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic research</topic><topic>Growth</topic><topic>HCC</topic><topic>Hepatoma</topic><topic>Humans</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - pathology</topic><topic>Male</topic><topic>Mice, Nude</topic><topic>Middle Aged</topic><topic>Neoplasm Invasiveness</topic><topic>Physiological aspects</topic><topic>qRT‐PCR</topic><topic>Reproducibility of Results</topic><topic>RNA</topic><topic>RNA - genetics</topic><topic>RNA - metabolism</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>RNA‐seq</topic><topic>ROC Curve</topic><topic>Sequence Analysis, RNA</topic><topic>Signal Transduction - genetics</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>ZKSCAN1</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yao, Zhicheng</creatorcontrib><creatorcontrib>Luo, Jingyan</creatorcontrib><creatorcontrib>Hu, Kunpeng</creatorcontrib><creatorcontrib>Lin, Jizong</creatorcontrib><creatorcontrib>Huang, He</creatorcontrib><creatorcontrib>Wang, Qiangliang</creatorcontrib><creatorcontrib>Zhang, Peng</creatorcontrib><creatorcontrib>Xiong, Zhiyong</creatorcontrib><creatorcontrib>He, Chonghua</creatorcontrib><creatorcontrib>Huang, Zejian</creatorcontrib><creatorcontrib>Liu, Bo</creatorcontrib><creatorcontrib>Yang, Yang</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yao, Zhicheng</au><au>Luo, Jingyan</au><au>Hu, Kunpeng</au><au>Lin, Jizong</au><au>Huang, He</au><au>Wang, Qiangliang</au><au>Zhang, Peng</au><au>Xiong, Zhiyong</au><au>He, Chonghua</au><au>Huang, Zejian</au><au>Liu, Bo</au><au>Yang, Yang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ZKSCAN1 gene and its related circular RNA (circZKSCAN1) both inhibit hepatocellular carcinoma cell growth, migration, and invasion but through different signaling pathways</atitle><jtitle>Molecular oncology</jtitle><addtitle>Mol Oncol</addtitle><date>2017-04</date><risdate>2017</risdate><volume>11</volume><issue>4</issue><spage>422</spage><epage>437</epage><pages>422-437</pages><issn>1574-7891</issn><eissn>1878-0261</eissn><abstract>There is increasing evidence that circular RNA (circRNA) are involved in cancer development, but the regulation and function of human circRNA remain largely unknown. In this study, we demonstrated that ZKSCAN1, a zinc finger family gene, is expressed in both linear and circular (circZKSCAN1) forms of RNA in human hepatocellular carcinoma (HCC) tissues and cell lines. Here, we analyzed a cohort of 102 patients and found that expression of both ZKSCAN1mRNA and circZKSCAN1 was significantly lower (P < 0.05) in the HCC samples compared with that in matched adjacent nontumorous tissues by reverse transcription PCR (RT‐PCR). The low expression level of ZKSCAN1 was only associated with tumor size (P = 0.032), while the cirZKSCAN1 levels varied in patients with different tumor numbers (P < 0.01), cirrhosis (P = 0.031), vascular invasion (P = 0.002), or microscopic vascular invasion (P = 0.002), as well as with the tumor grade (P < 0.001). Silencing both ZKSCAN1mRNA and circZKSCAN1 promoted cell proliferation, migration, and invasion. In contrast, overexpression of both forms of RNA repressed HCC progression in vivo and in vitro. Silencing or overexpression of both forms of RNA did not interfere with each other. RNA‐seq revealed a very different molecular basis for the observed effects; ZKSCAN1mRNA mainly regulated cellular metabolism, while circZKSCAN1 mediated several cancer‐related signaling pathways, suggesting a nonredundant role for ZKSCAN1mRNA and circRNA. In conclusion, our results revealed two post‐translational products (ZKSCAN1mRNA and circZKSCAN1) that cooperated closely with one another to inhibit growth, migration, and invasion of HCC. cirZKSCAN1 might be a useful marker for the diagnosis of HCC.
Circular RNA have recently been shown to play a regulatory role in disease. We investigated the role of circRNA transcribed from ZKSCAN1, a member of the zinc finger family. Our results revealed two post‐translational products (ZKSCAN1 mRNA and circZKSCAN1) that cooperated closely with one another to inhibit cancer growth migration and invasion, but which affected different signaling pathways.</abstract><cop>United States</cop><pub>John Wiley & Sons, Inc</pub><pmid>28211215</pmid><doi>10.1002/1878-0261.12045</doi><tpages>16</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Base Sequence Cancer Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - pathology Cell Line, Tumor Cell Movement - genetics Cell Proliferation - genetics circular RNA Demography Down-Regulation - genetics Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Genes Genetic aspects Genetic research Growth HCC Hepatoma Humans Liver Neoplasms - genetics Liver Neoplasms - pathology Male Mice, Nude Middle Aged Neoplasm Invasiveness Physiological aspects qRT‐PCR Reproducibility of Results RNA RNA - genetics RNA - metabolism RNA, Messenger - genetics RNA, Messenger - metabolism RNA‐seq ROC Curve Sequence Analysis, RNA Signal Transduction - genetics Transcription Factors - genetics Transcription Factors - metabolism ZKSCAN1 |
| title | ZKSCAN1 gene and its related circular RNA (circZKSCAN1) both inhibit hepatocellular carcinoma cell growth, migration, and invasion but through different signaling pathways |
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