microRNA-494 is a potential prognostic marker and inhibits cellular proliferation, migration and invasion by targeting SIRT1 in epithelial ovarian cancer
Ovarian cancer is one of the most common types of gynecological malignancy worldwide, and is the fourth leading cause of cancer-associated mortality among women. Despite improvements in therapeutic treatments, the prognosis for epithelial ovarian cancer (EOC) remains poor, mainly due to the rapid gr...
Gespeichert in:
Veröffentlicht in: | Oncology letters 2017-09, Vol.14 (3), p.3177-3184 |
---|---|
Hauptverfasser: | , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 3184 |
---|---|
container_issue | 3 |
container_start_page | 3177 |
container_title | Oncology letters |
container_volume | 14 |
creator | Yang, Aijun Wang, Xuenan Yu, Chunna Jin, Zhenzhen Wei, Lingxia Cao, Jinghe Wang, Qin Zhang, Min Zhang, Lin Zhang, Lei Hao, Cuifang |
description | Ovarian cancer is one of the most common types of gynecological malignancy worldwide, and is the fourth leading cause of cancer-associated mortality among women. Despite improvements in therapeutic treatments, the prognosis for epithelial ovarian cancer (EOC) remains poor, mainly due to the rapid growth and metastasis of ovarian cancer tumors. An increasing number of studies have indicated that microRNAs (miRNAs) are involved in the carcinogenesis and progression of human cancer, suggesting that miRNAs may be used in clinical prognosis and as a therapeutic target in EOC. The aim of the present study was to investigate the expression levels of miRNA-494 in EOC tissues and cell lines. The clinical significance of miRNA-494 in patients with EOC was also evaluated. The results demonstrated that miRNA-494 was significantly downregulated in EOC tissues and cell lines. Low expression levels of miRNA-494 were associated with poor prognostic features, including International Federation of Gynecology and Obstetrics stage, tumor size and lymph node metastasis. In vitro functional studies demonstrated that overexpression of miRNA-494 inhibited proliferation, migration and invasion in EOC cells. By contrast, knockdown of miRNA-494 enhanced cell growth, migration and invasion in EOC cells. Notably, sirtuin 1 (SIRT1) was identified as a direct target of miRNA-494 in EOC. Furthermore, MTT, cell migration and invasion assays verified that EOC cell proliferation, migration and invasion were completely restored with forced miRNA-494 expression and SIRT1 restoration. Together, these findings suggest that miRNA-494 is a potential prognostic marker, and may provide novel therapeutic regimens of targeted therapy for EOC. |
doi_str_mv | 10.3892/ol.2017.6501 |
format | Article |
fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5588040</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A511212875</galeid><sourcerecordid>A511212875</sourcerecordid><originalsourceid>FETCH-LOGICAL-c539t-ddc0b5635b8222f0f3cde3d9f3e909ea2a7ab44a1837f89f5ab67a40c3a359b73</originalsourceid><addsrcrecordid>eNptkk1v3CAQhq2qVROlufVcIbWqeoi3gI0Nl0qrqB-RVo2Upmc0xthLyoID9kr5Kf23xd3tNlsVDgzwzItmeLPsJcGLggv63tsFxaReVAyTJ9kpqQXNCeb06SGuy5PsPMY7nAarCOfV8-yEptwaV8Vp9nNjVPA3X5d5KUpkIgI0-FG70YBFQ_C983E0Cm0g_NABgWuRcWvTmDEipa2dLISZs6bTAUbj3QXamH4X7vEtxHnTPKARQq9H43r07ermlqQ7pAczrrWdn_NbCAYcUuCUDi-yZx3YqM_361n2_dPH28sv-er689XlcpUrVogxb1uFG1YVrOGU0g53hWp10Yqu0AILDRRqaMoSCC_qjouOQVPVUGJVQMFEUxdn2Yed7jA1G92qVHsAK4dgUs0P0oORxzfOrGXvt5IxznGJk8C7vUDw95OOo9yYOPcGnPZTlESUBItKMJ7Q1_-gd34KLpU3U5SwUojyL9WD1dK4zqd31Swql4wQSiivWaIW_6HSbHX6U-90Z9L5UcLbRwlrDXZcR2-n-afiMXixA5MzYgy6OzSDYDnbTnorZ9vJ2XYJf_W4gQf4j8kS8GYHxCEZwrQ-HpjrVY7T_K3zC0an3y4</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1942154994</pqid></control><display><type>article</type><title>microRNA-494 is a potential prognostic marker and inhibits cellular proliferation, migration and invasion by targeting SIRT1 in epithelial ovarian cancer</title><source>Spandidos Publications Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Yang, Aijun ; Wang, Xuenan ; Yu, Chunna ; Jin, Zhenzhen ; Wei, Lingxia ; Cao, Jinghe ; Wang, Qin ; Zhang, Min ; Zhang, Lin ; Zhang, Lei ; Hao, Cuifang</creator><creatorcontrib>Yang, Aijun ; Wang, Xuenan ; Yu, Chunna ; Jin, Zhenzhen ; Wei, Lingxia ; Cao, Jinghe ; Wang, Qin ; Zhang, Min ; Zhang, Lin ; Zhang, Lei ; Hao, Cuifang</creatorcontrib><description>Ovarian cancer is one of the most common types of gynecological malignancy worldwide, and is the fourth leading cause of cancer-associated mortality among women. Despite improvements in therapeutic treatments, the prognosis for epithelial ovarian cancer (EOC) remains poor, mainly due to the rapid growth and metastasis of ovarian cancer tumors. An increasing number of studies have indicated that microRNAs (miRNAs) are involved in the carcinogenesis and progression of human cancer, suggesting that miRNAs may be used in clinical prognosis and as a therapeutic target in EOC. The aim of the present study was to investigate the expression levels of miRNA-494 in EOC tissues and cell lines. The clinical significance of miRNA-494 in patients with EOC was also evaluated. The results demonstrated that miRNA-494 was significantly downregulated in EOC tissues and cell lines. Low expression levels of miRNA-494 were associated with poor prognostic features, including International Federation of Gynecology and Obstetrics stage, tumor size and lymph node metastasis. In vitro functional studies demonstrated that overexpression of miRNA-494 inhibited proliferation, migration and invasion in EOC cells. By contrast, knockdown of miRNA-494 enhanced cell growth, migration and invasion in EOC cells. Notably, sirtuin 1 (SIRT1) was identified as a direct target of miRNA-494 in EOC. Furthermore, MTT, cell migration and invasion assays verified that EOC cell proliferation, migration and invasion were completely restored with forced miRNA-494 expression and SIRT1 restoration. Together, these findings suggest that miRNA-494 is a potential prognostic marker, and may provide novel therapeutic regimens of targeted therapy for EOC.</description><identifier>ISSN: 1792-1074</identifier><identifier>EISSN: 1792-1082</identifier><identifier>DOI: 10.3892/ol.2017.6501</identifier><identifier>PMID: 28927063</identifier><language>eng</language><publisher>Greece: D.A. Spandidos</publisher><subject>Apoptosis ; Cancer therapies ; Care and treatment ; Cell culture ; Cell cycle ; Cell growth ; Development and progression ; Epithelial tumors ; Gene expression ; Genetic aspects ; Gynecology ; Health aspects ; Lymphatic system ; Medical prognosis ; Metastasis ; MicroRNA ; microRNA-494 ; MicroRNAs ; Mortality ; Obstetrics ; Oncology ; Ovarian cancer ; Penicillin ; prognostic ; sirtuin 1 ; Studies ; Tumors</subject><ispartof>Oncology letters, 2017-09, Vol.14 (3), p.3177-3184</ispartof><rights>Copyright © 2017, Spandidos Publications</rights><rights>COPYRIGHT 2017 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2017</rights><rights>Copyright © 2017, Spandidos Publications 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c539t-ddc0b5635b8222f0f3cde3d9f3e909ea2a7ab44a1837f89f5ab67a40c3a359b73</citedby><cites>FETCH-LOGICAL-c539t-ddc0b5635b8222f0f3cde3d9f3e909ea2a7ab44a1837f89f5ab67a40c3a359b73</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/PMC5588040/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5588040/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,728,781,785,886,5572,27926,27927,53793,53795</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28927063$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Aijun</creatorcontrib><creatorcontrib>Wang, Xuenan</creatorcontrib><creatorcontrib>Yu, Chunna</creatorcontrib><creatorcontrib>Jin, Zhenzhen</creatorcontrib><creatorcontrib>Wei, Lingxia</creatorcontrib><creatorcontrib>Cao, Jinghe</creatorcontrib><creatorcontrib>Wang, Qin</creatorcontrib><creatorcontrib>Zhang, Min</creatorcontrib><creatorcontrib>Zhang, Lin</creatorcontrib><creatorcontrib>Zhang, Lei</creatorcontrib><creatorcontrib>Hao, Cuifang</creatorcontrib><title>microRNA-494 is a potential prognostic marker and inhibits cellular proliferation, migration and invasion by targeting SIRT1 in epithelial ovarian cancer</title><title>Oncology letters</title><addtitle>Oncol Lett</addtitle><description>Ovarian cancer is one of the most common types of gynecological malignancy worldwide, and is the fourth leading cause of cancer-associated mortality among women. Despite improvements in therapeutic treatments, the prognosis for epithelial ovarian cancer (EOC) remains poor, mainly due to the rapid growth and metastasis of ovarian cancer tumors. An increasing number of studies have indicated that microRNAs (miRNAs) are involved in the carcinogenesis and progression of human cancer, suggesting that miRNAs may be used in clinical prognosis and as a therapeutic target in EOC. The aim of the present study was to investigate the expression levels of miRNA-494 in EOC tissues and cell lines. The clinical significance of miRNA-494 in patients with EOC was also evaluated. The results demonstrated that miRNA-494 was significantly downregulated in EOC tissues and cell lines. Low expression levels of miRNA-494 were associated with poor prognostic features, including International Federation of Gynecology and Obstetrics stage, tumor size and lymph node metastasis. In vitro functional studies demonstrated that overexpression of miRNA-494 inhibited proliferation, migration and invasion in EOC cells. By contrast, knockdown of miRNA-494 enhanced cell growth, migration and invasion in EOC cells. Notably, sirtuin 1 (SIRT1) was identified as a direct target of miRNA-494 in EOC. Furthermore, MTT, cell migration and invasion assays verified that EOC cell proliferation, migration and invasion were completely restored with forced miRNA-494 expression and SIRT1 restoration. Together, these findings suggest that miRNA-494 is a potential prognostic marker, and may provide novel therapeutic regimens of targeted therapy for EOC.</description><subject>Apoptosis</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>Cell culture</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Development and progression</subject><subject>Epithelial tumors</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Gynecology</subject><subject>Health aspects</subject><subject>Lymphatic system</subject><subject>Medical prognosis</subject><subject>Metastasis</subject><subject>MicroRNA</subject><subject>microRNA-494</subject><subject>MicroRNAs</subject><subject>Mortality</subject><subject>Obstetrics</subject><subject>Oncology</subject><subject>Ovarian cancer</subject><subject>Penicillin</subject><subject>prognostic</subject><subject>sirtuin 1</subject><subject>Studies</subject><subject>Tumors</subject><issn>1792-1074</issn><issn>1792-1082</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNptkk1v3CAQhq2qVROlufVcIbWqeoi3gI0Nl0qrqB-RVo2Upmc0xthLyoID9kr5Kf23xd3tNlsVDgzwzItmeLPsJcGLggv63tsFxaReVAyTJ9kpqQXNCeb06SGuy5PsPMY7nAarCOfV8-yEptwaV8Vp9nNjVPA3X5d5KUpkIgI0-FG70YBFQ_C983E0Cm0g_NABgWuRcWvTmDEipa2dLISZs6bTAUbj3QXamH4X7vEtxHnTPKARQq9H43r07ermlqQ7pAczrrWdn_NbCAYcUuCUDi-yZx3YqM_361n2_dPH28sv-er689XlcpUrVogxb1uFG1YVrOGU0g53hWp10Yqu0AILDRRqaMoSCC_qjouOQVPVUGJVQMFEUxdn2Yed7jA1G92qVHsAK4dgUs0P0oORxzfOrGXvt5IxznGJk8C7vUDw95OOo9yYOPcGnPZTlESUBItKMJ7Q1_-gd34KLpU3U5SwUojyL9WD1dK4zqd31Swql4wQSiivWaIW_6HSbHX6U-90Z9L5UcLbRwlrDXZcR2-n-afiMXixA5MzYgy6OzSDYDnbTnorZ9vJ2XYJf_W4gQf4j8kS8GYHxCEZwrQ-HpjrVY7T_K3zC0an3y4</recordid><startdate>20170901</startdate><enddate>20170901</enddate><creator>Yang, Aijun</creator><creator>Wang, Xuenan</creator><creator>Yu, Chunna</creator><creator>Jin, Zhenzhen</creator><creator>Wei, Lingxia</creator><creator>Cao, Jinghe</creator><creator>Wang, Qin</creator><creator>Zhang, Min</creator><creator>Zhang, Lin</creator><creator>Zhang, Lei</creator><creator>Hao, Cuifang</creator><general>D.A. Spandidos</general><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170901</creationdate><title>microRNA-494 is a potential prognostic marker and inhibits cellular proliferation, migration and invasion by targeting SIRT1 in epithelial ovarian cancer</title><author>Yang, Aijun ; Wang, Xuenan ; Yu, Chunna ; Jin, Zhenzhen ; Wei, Lingxia ; Cao, Jinghe ; Wang, Qin ; Zhang, Min ; Zhang, Lin ; Zhang, Lei ; Hao, Cuifang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c539t-ddc0b5635b8222f0f3cde3d9f3e909ea2a7ab44a1837f89f5ab67a40c3a359b73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Apoptosis</topic><topic>Cancer therapies</topic><topic>Care and treatment</topic><topic>Cell culture</topic><topic>Cell cycle</topic><topic>Cell growth</topic><topic>Development and progression</topic><topic>Epithelial tumors</topic><topic>Gene expression</topic><topic>Genetic aspects</topic><topic>Gynecology</topic><topic>Health aspects</topic><topic>Lymphatic system</topic><topic>Medical prognosis</topic><topic>Metastasis</topic><topic>MicroRNA</topic><topic>microRNA-494</topic><topic>MicroRNAs</topic><topic>Mortality</topic><topic>Obstetrics</topic><topic>Oncology</topic><topic>Ovarian cancer</topic><topic>Penicillin</topic><topic>prognostic</topic><topic>sirtuin 1</topic><topic>Studies</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Aijun</creatorcontrib><creatorcontrib>Wang, Xuenan</creatorcontrib><creatorcontrib>Yu, Chunna</creatorcontrib><creatorcontrib>Jin, Zhenzhen</creatorcontrib><creatorcontrib>Wei, Lingxia</creatorcontrib><creatorcontrib>Cao, Jinghe</creatorcontrib><creatorcontrib>Wang, Qin</creatorcontrib><creatorcontrib>Zhang, Min</creatorcontrib><creatorcontrib>Zhang, Lin</creatorcontrib><creatorcontrib>Zhang, Lei</creatorcontrib><creatorcontrib>Hao, Cuifang</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>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>British Nursing Database</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</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>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><jtitle>Oncology letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Aijun</au><au>Wang, Xuenan</au><au>Yu, Chunna</au><au>Jin, Zhenzhen</au><au>Wei, Lingxia</au><au>Cao, Jinghe</au><au>Wang, Qin</au><au>Zhang, Min</au><au>Zhang, Lin</au><au>Zhang, Lei</au><au>Hao, Cuifang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>microRNA-494 is a potential prognostic marker and inhibits cellular proliferation, migration and invasion by targeting SIRT1 in epithelial ovarian cancer</atitle><jtitle>Oncology letters</jtitle><addtitle>Oncol Lett</addtitle><date>2017-09-01</date><risdate>2017</risdate><volume>14</volume><issue>3</issue><spage>3177</spage><epage>3184</epage><pages>3177-3184</pages><issn>1792-1074</issn><eissn>1792-1082</eissn><abstract>Ovarian cancer is one of the most common types of gynecological malignancy worldwide, and is the fourth leading cause of cancer-associated mortality among women. Despite improvements in therapeutic treatments, the prognosis for epithelial ovarian cancer (EOC) remains poor, mainly due to the rapid growth and metastasis of ovarian cancer tumors. An increasing number of studies have indicated that microRNAs (miRNAs) are involved in the carcinogenesis and progression of human cancer, suggesting that miRNAs may be used in clinical prognosis and as a therapeutic target in EOC. The aim of the present study was to investigate the expression levels of miRNA-494 in EOC tissues and cell lines. The clinical significance of miRNA-494 in patients with EOC was also evaluated. The results demonstrated that miRNA-494 was significantly downregulated in EOC tissues and cell lines. Low expression levels of miRNA-494 were associated with poor prognostic features, including International Federation of Gynecology and Obstetrics stage, tumor size and lymph node metastasis. In vitro functional studies demonstrated that overexpression of miRNA-494 inhibited proliferation, migration and invasion in EOC cells. By contrast, knockdown of miRNA-494 enhanced cell growth, migration and invasion in EOC cells. Notably, sirtuin 1 (SIRT1) was identified as a direct target of miRNA-494 in EOC. Furthermore, MTT, cell migration and invasion assays verified that EOC cell proliferation, migration and invasion were completely restored with forced miRNA-494 expression and SIRT1 restoration. Together, these findings suggest that miRNA-494 is a potential prognostic marker, and may provide novel therapeutic regimens of targeted therapy for EOC.</abstract><cop>Greece</cop><pub>D.A. Spandidos</pub><pmid>28927063</pmid><doi>10.3892/ol.2017.6501</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1792-1074 |
ispartof | Oncology letters, 2017-09, Vol.14 (3), p.3177-3184 |
issn | 1792-1074 1792-1082 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5588040 |
source | Spandidos Publications Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
subjects | Apoptosis Cancer therapies Care and treatment Cell culture Cell cycle Cell growth Development and progression Epithelial tumors Gene expression Genetic aspects Gynecology Health aspects Lymphatic system Medical prognosis Metastasis MicroRNA microRNA-494 MicroRNAs Mortality Obstetrics Oncology Ovarian cancer Penicillin prognostic sirtuin 1 Studies Tumors |
title | microRNA-494 is a potential prognostic marker and inhibits cellular proliferation, migration and invasion by targeting SIRT1 in epithelial ovarian cancer |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-18T06%3A05%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=microRNA-494%20is%20a%20potential%20prognostic%20marker%20and%20inhibits%20cellular%20proliferation,%20migration%20and%20invasion%20by%20targeting%20SIRT1%20in%20epithelial%20ovarian%20cancer&rft.jtitle=Oncology%20letters&rft.au=Yang,%20Aijun&rft.date=2017-09-01&rft.volume=14&rft.issue=3&rft.spage=3177&rft.epage=3184&rft.pages=3177-3184&rft.issn=1792-1074&rft.eissn=1792-1082&rft_id=info:doi/10.3892/ol.2017.6501&rft_dat=%3Cgale_pubme%3EA511212875%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1942154994&rft_id=info:pmid/28927063&rft_galeid=A511212875&rfr_iscdi=true |