Long noncoding RNA actin filament‐associated protein 1 antisense RNA 1 promotes malignant phenotype through binding with lysine‐specific demethylase 1 and repressing HMG box‐containing protein 1 in non‐small‐cell lung cancer
The number of documented long noncoding RNAs (lncRNAs) has dramatically increased, and their biological functions and underlying mechanisms in pathological processes, especially cancer, remain to be elucidated. Actin filament‐associated protein 1 antisense RNA 1 (AFAP1‐AS1) is a 6810‐nt lncRNA locat...
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| Veröffentlicht in: | Cancer science 2019-07, Vol.110 (7), p.2211-2225 |
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| creator | Yu, Shanxun Yang, Daolu Ye, Yunyao Liu, Pei Chen, Zhenyao Lei, Tianyao Pu, Jiaze Liu, Longfa Wang, Zhaoxia |
| description | The number of documented long noncoding RNAs (lncRNAs) has dramatically increased, and their biological functions and underlying mechanisms in pathological processes, especially cancer, remain to be elucidated. Actin filament‐associated protein 1 antisense RNA 1 (AFAP1‐AS1) is a 6810‐nt lncRNA located on chromosome 4p16.1 that was first reported to be upregulated in esophageal adenocarcinoma tissues and cell lines. Here we reported that AFAP1‐AS1, recruiting and binding to lysine‐specific demethylase 1 (LSD1), was generally overexpressed in human non‐small‐cell lung cancer (NSCLC) tissues using quantitative real‐time PCR. Higher AFAP1‐AS1 expression was significantly correlated with larger tumor size (P = .008), lymph node metastasis (P = .025), higher TNM stage (P = .024), and worse overall survival in NSCLC patients. In vitro experiments revealed that AFAP1‐AS1 downregulation inhibited cell migration and induced apoptosis; AFAP1‐AS1 knockdown also hindered tumorigenesis in vivo. Moreover, mechanistic investigations including RNA immunoprecipitation and ChIP assays validated that AFAP1‐AS1 repressed HMG box‐containing protein 1 (HBP1) expression by recruiting LSD1 to the HBP1 promoter regions in PC‐9 and H1975 cells. Furthermore, HBP1 functions as a tumor suppressor, and its ectopic expression hindered cell proliferation. Rescue assays determined that the oncogenic effect of AFAP1‐AS1 is partially dependent on the epigenetic silencing of HBP1. In conclusion, our results indicate that AFAP1‐AS1 is carcinogenic and that the AFAP1‐AS1/LSD1/HBP1 axis could constitute a new therapeutic direction for NSCLC.
The study provides the available evidence that both actin filament‐associated protein 1 antisense RNA 1 (AFAP1‐AS1) and HMG box‐containing protein 1 (HBP1) play crucial roles in non‐small‐cell lung cancer (NSCLC) development and progression. The AFAP1‐AS1/LSD1/HBP1 axis could serve as a potential target for therapy in NSCLC. |
| doi_str_mv | 10.1111/cas.14039 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6609801</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2251879984</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4679-21c9fdac655ebbd3abbaa115cf135dc12d8a6b78acdfc2663320c61074d7c0c13</originalsourceid><addsrcrecordid>eNp1ks9u1DAQxiNERUvhwAsgS5w4pLXjrBNfkFYraJGWIvHnbDljZ-PKsYPtbdkbj8AzcuQpcHZLgQM-2CN_v_lmbE1RPCP4jOR1DjKekRpT_qA4IbTmZYMxe7iPm5JjWh0Xj2O8xpiymtePimNKMOMtpyfFz7V3G-S8A69Mjj5cLZGEZBzqjZWjdunHt-8yRg9GJq3QFHzSWSVIumSidlHvc8isjFmLaJTWbFyW0TRo59Nu0igNwW83A-qM25e5NWlAdheN09k_ThpMbwApPeo07KzMrnMFhYKego5xzrl8d4E6_zXz4F2Sxs2Xf_rJW37G7JYbsDOlrUV2myGQDnR4Uhz10kb99O48LT6_ef1pdVmu31-8XS3XJdSs4WVFgPdKAlssdNcpKrtOSkIW0BO6UEAq1UrWNa0E1UPFGKUVBkZwU6sGMBB6Wrw6-E7bbtQK8h8GacUUzCjDTnhpxL-KM4PY-BvBGOYtng1e3BkE_2WrYxLXfhtc7llU1YK0DedtnamXBwqCjzHo_r4CwWIeC5HHQuzHIrPP_27pnvw9Bxk4PwC3xurd_53EavnxYPkLwsTN5A</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2251879984</pqid></control><display><type>article</type><title>Long noncoding RNA actin filament‐associated protein 1 antisense RNA 1 promotes malignant phenotype through binding with lysine‐specific demethylase 1 and repressing HMG box‐containing protein 1 in non‐small‐cell lung cancer</title><source>Wiley Online Library - AutoHoldings Journals</source><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Wiley Online Library Open Access</source><source>PubMed Central</source><creator>Yu, Shanxun ; Yang, Daolu ; Ye, Yunyao ; Liu, Pei ; Chen, Zhenyao ; Lei, Tianyao ; Pu, Jiaze ; Liu, Longfa ; Wang, Zhaoxia</creator><creatorcontrib>Yu, Shanxun ; Yang, Daolu ; Ye, Yunyao ; Liu, Pei ; Chen, Zhenyao ; Lei, Tianyao ; Pu, Jiaze ; Liu, Longfa ; Wang, Zhaoxia</creatorcontrib><description>The number of documented long noncoding RNAs (lncRNAs) has dramatically increased, and their biological functions and underlying mechanisms in pathological processes, especially cancer, remain to be elucidated. Actin filament‐associated protein 1 antisense RNA 1 (AFAP1‐AS1) is a 6810‐nt lncRNA located on chromosome 4p16.1 that was first reported to be upregulated in esophageal adenocarcinoma tissues and cell lines. Here we reported that AFAP1‐AS1, recruiting and binding to lysine‐specific demethylase 1 (LSD1), was generally overexpressed in human non‐small‐cell lung cancer (NSCLC) tissues using quantitative real‐time PCR. Higher AFAP1‐AS1 expression was significantly correlated with larger tumor size (P = .008), lymph node metastasis (P = .025), higher TNM stage (P = .024), and worse overall survival in NSCLC patients. In vitro experiments revealed that AFAP1‐AS1 downregulation inhibited cell migration and induced apoptosis; AFAP1‐AS1 knockdown also hindered tumorigenesis in vivo. Moreover, mechanistic investigations including RNA immunoprecipitation and ChIP assays validated that AFAP1‐AS1 repressed HMG box‐containing protein 1 (HBP1) expression by recruiting LSD1 to the HBP1 promoter regions in PC‐9 and H1975 cells. Furthermore, HBP1 functions as a tumor suppressor, and its ectopic expression hindered cell proliferation. Rescue assays determined that the oncogenic effect of AFAP1‐AS1 is partially dependent on the epigenetic silencing of HBP1. In conclusion, our results indicate that AFAP1‐AS1 is carcinogenic and that the AFAP1‐AS1/LSD1/HBP1 axis could constitute a new therapeutic direction for NSCLC.
The study provides the available evidence that both actin filament‐associated protein 1 antisense RNA 1 (AFAP1‐AS1) and HMG box‐containing protein 1 (HBP1) play crucial roles in non‐small‐cell lung cancer (NSCLC) development and progression. The AFAP1‐AS1/LSD1/HBP1 axis could serve as a potential target for therapy in NSCLC.</description><identifier>ISSN: 1347-9032</identifier><identifier>EISSN: 1349-7006</identifier><identifier>DOI: 10.1111/cas.14039</identifier><identifier>PMID: 31069893</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>A549 Cells ; Actin ; Adenocarcinoma ; AFAP1‐AS1 ; Animals ; Antisense RNA ; Apoptosis ; Cancer therapies ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - pathology ; Cell cycle ; Cell growth ; Cell Line, Tumor ; Cell migration ; Cell Proliferation ; Cell Survival ; Chemotherapy ; Chromosome 4 ; Deoxyribonucleic acid ; DNA ; Ectopic expression ; Epigenesis, Genetic ; Esophagus ; Female ; Gastric cancer ; Gene expression ; Genomes ; HBP1 ; High Mobility Group Proteins - genetics ; Histone Demethylases - genetics ; Humans ; Immunoprecipitation ; long noncoding RNA ; LSD1 ; Lung cancer ; Lung Neoplasms - genetics ; Lung Neoplasms - pathology ; Lymph nodes ; Lymphatic system ; Lysine ; Male ; Metastases ; Metastasis ; Mice ; Neoplasm Transplantation ; Non-small cell lung carcinoma ; non‐small‐cell lung cancer ; Original ; Phenotypes ; Prognosis ; Prostate cancer ; Proteins ; Repressor Proteins - genetics ; Ribonucleic acid ; RNA ; RNA, Long Noncoding - genetics ; Studies ; Survival Analysis ; Tumor cell lines ; Tumor suppressor genes ; Tumorigenesis</subject><ispartof>Cancer science, 2019-07, Vol.110 (7), p.2211-2225</ispartof><rights>2019 The Authors. published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>2019. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4679-21c9fdac655ebbd3abbaa115cf135dc12d8a6b78acdfc2663320c61074d7c0c13</citedby><cites>FETCH-LOGICAL-c4679-21c9fdac655ebbd3abbaa115cf135dc12d8a6b78acdfc2663320c61074d7c0c13</cites><orcidid>0000-0002-1893-371X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609801/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609801/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,1417,11562,27924,27925,45574,45575,46052,46476,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31069893$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yu, Shanxun</creatorcontrib><creatorcontrib>Yang, Daolu</creatorcontrib><creatorcontrib>Ye, Yunyao</creatorcontrib><creatorcontrib>Liu, Pei</creatorcontrib><creatorcontrib>Chen, Zhenyao</creatorcontrib><creatorcontrib>Lei, Tianyao</creatorcontrib><creatorcontrib>Pu, Jiaze</creatorcontrib><creatorcontrib>Liu, Longfa</creatorcontrib><creatorcontrib>Wang, Zhaoxia</creatorcontrib><title>Long noncoding RNA actin filament‐associated protein 1 antisense RNA 1 promotes malignant phenotype through binding with lysine‐specific demethylase 1 and repressing HMG box‐containing protein 1 in non‐small‐cell lung cancer</title><title>Cancer science</title><addtitle>Cancer Sci</addtitle><description>The number of documented long noncoding RNAs (lncRNAs) has dramatically increased, and their biological functions and underlying mechanisms in pathological processes, especially cancer, remain to be elucidated. Actin filament‐associated protein 1 antisense RNA 1 (AFAP1‐AS1) is a 6810‐nt lncRNA located on chromosome 4p16.1 that was first reported to be upregulated in esophageal adenocarcinoma tissues and cell lines. Here we reported that AFAP1‐AS1, recruiting and binding to lysine‐specific demethylase 1 (LSD1), was generally overexpressed in human non‐small‐cell lung cancer (NSCLC) tissues using quantitative real‐time PCR. Higher AFAP1‐AS1 expression was significantly correlated with larger tumor size (P = .008), lymph node metastasis (P = .025), higher TNM stage (P = .024), and worse overall survival in NSCLC patients. In vitro experiments revealed that AFAP1‐AS1 downregulation inhibited cell migration and induced apoptosis; AFAP1‐AS1 knockdown also hindered tumorigenesis in vivo. Moreover, mechanistic investigations including RNA immunoprecipitation and ChIP assays validated that AFAP1‐AS1 repressed HMG box‐containing protein 1 (HBP1) expression by recruiting LSD1 to the HBP1 promoter regions in PC‐9 and H1975 cells. Furthermore, HBP1 functions as a tumor suppressor, and its ectopic expression hindered cell proliferation. Rescue assays determined that the oncogenic effect of AFAP1‐AS1 is partially dependent on the epigenetic silencing of HBP1. In conclusion, our results indicate that AFAP1‐AS1 is carcinogenic and that the AFAP1‐AS1/LSD1/HBP1 axis could constitute a new therapeutic direction for NSCLC.
The study provides the available evidence that both actin filament‐associated protein 1 antisense RNA 1 (AFAP1‐AS1) and HMG box‐containing protein 1 (HBP1) play crucial roles in non‐small‐cell lung cancer (NSCLC) development and progression. The AFAP1‐AS1/LSD1/HBP1 axis could serve as a potential target for therapy in NSCLC.</description><subject>A549 Cells</subject><subject>Actin</subject><subject>Adenocarcinoma</subject><subject>AFAP1‐AS1</subject><subject>Animals</subject><subject>Antisense RNA</subject><subject>Apoptosis</subject><subject>Cancer therapies</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - pathology</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell migration</subject><subject>Cell Proliferation</subject><subject>Cell Survival</subject><subject>Chemotherapy</subject><subject>Chromosome 4</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Ectopic expression</subject><subject>Epigenesis, Genetic</subject><subject>Esophagus</subject><subject>Female</subject><subject>Gastric cancer</subject><subject>Gene expression</subject><subject>Genomes</subject><subject>HBP1</subject><subject>High Mobility Group Proteins - genetics</subject><subject>Histone Demethylases - genetics</subject><subject>Humans</subject><subject>Immunoprecipitation</subject><subject>long noncoding RNA</subject><subject>LSD1</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - pathology</subject><subject>Lymph nodes</subject><subject>Lymphatic system</subject><subject>Lysine</subject><subject>Male</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Neoplasm Transplantation</subject><subject>Non-small cell lung carcinoma</subject><subject>non‐small‐cell lung cancer</subject><subject>Original</subject><subject>Phenotypes</subject><subject>Prognosis</subject><subject>Prostate cancer</subject><subject>Proteins</subject><subject>Repressor Proteins - genetics</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Long Noncoding - genetics</subject><subject>Studies</subject><subject>Survival Analysis</subject><subject>Tumor cell lines</subject><subject>Tumor suppressor genes</subject><subject>Tumorigenesis</subject><issn>1347-9032</issn><issn>1349-7006</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1ks9u1DAQxiNERUvhwAsgS5w4pLXjrBNfkFYraJGWIvHnbDljZ-PKsYPtbdkbj8AzcuQpcHZLgQM-2CN_v_lmbE1RPCP4jOR1DjKekRpT_qA4IbTmZYMxe7iPm5JjWh0Xj2O8xpiymtePimNKMOMtpyfFz7V3G-S8A69Mjj5cLZGEZBzqjZWjdunHt-8yRg9GJq3QFHzSWSVIumSidlHvc8isjFmLaJTWbFyW0TRo59Nu0igNwW83A-qM25e5NWlAdheN09k_ThpMbwApPeo07KzMrnMFhYKego5xzrl8d4E6_zXz4F2Sxs2Xf_rJW37G7JYbsDOlrUV2myGQDnR4Uhz10kb99O48LT6_ef1pdVmu31-8XS3XJdSs4WVFgPdKAlssdNcpKrtOSkIW0BO6UEAq1UrWNa0E1UPFGKUVBkZwU6sGMBB6Wrw6-E7bbtQK8h8GacUUzCjDTnhpxL-KM4PY-BvBGOYtng1e3BkE_2WrYxLXfhtc7llU1YK0DedtnamXBwqCjzHo_r4CwWIeC5HHQuzHIrPP_27pnvw9Bxk4PwC3xurd_53EavnxYPkLwsTN5A</recordid><startdate>201907</startdate><enddate>201907</enddate><creator>Yu, Shanxun</creator><creator>Yang, Daolu</creator><creator>Ye, Yunyao</creator><creator>Liu, Pei</creator><creator>Chen, Zhenyao</creator><creator>Lei, Tianyao</creator><creator>Pu, Jiaze</creator><creator>Liu, Longfa</creator><creator>Wang, Zhaoxia</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1893-371X</orcidid></search><sort><creationdate>201907</creationdate><title>Long noncoding RNA actin filament‐associated protein 1 antisense RNA 1 promotes malignant phenotype through binding with lysine‐specific demethylase 1 and repressing HMG box‐containing protein 1 in non‐small‐cell lung cancer</title><author>Yu, Shanxun ; Yang, Daolu ; Ye, Yunyao ; Liu, Pei ; Chen, Zhenyao ; Lei, Tianyao ; Pu, Jiaze ; Liu, Longfa ; Wang, Zhaoxia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4679-21c9fdac655ebbd3abbaa115cf135dc12d8a6b78acdfc2663320c61074d7c0c13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>A549 Cells</topic><topic>Actin</topic><topic>Adenocarcinoma</topic><topic>AFAP1‐AS1</topic><topic>Animals</topic><topic>Antisense RNA</topic><topic>Apoptosis</topic><topic>Cancer therapies</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - pathology</topic><topic>Cell cycle</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell migration</topic><topic>Cell Proliferation</topic><topic>Cell Survival</topic><topic>Chemotherapy</topic><topic>Chromosome 4</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Ectopic expression</topic><topic>Epigenesis, Genetic</topic><topic>Esophagus</topic><topic>Female</topic><topic>Gastric cancer</topic><topic>Gene expression</topic><topic>Genomes</topic><topic>HBP1</topic><topic>High Mobility Group Proteins - genetics</topic><topic>Histone Demethylases - genetics</topic><topic>Humans</topic><topic>Immunoprecipitation</topic><topic>long noncoding RNA</topic><topic>LSD1</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - pathology</topic><topic>Lymph nodes</topic><topic>Lymphatic system</topic><topic>Lysine</topic><topic>Male</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Neoplasm Transplantation</topic><topic>Non-small cell lung carcinoma</topic><topic>non‐small‐cell lung cancer</topic><topic>Original</topic><topic>Phenotypes</topic><topic>Prognosis</topic><topic>Prostate cancer</topic><topic>Proteins</topic><topic>Repressor Proteins - genetics</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA, Long Noncoding - genetics</topic><topic>Studies</topic><topic>Survival Analysis</topic><topic>Tumor cell lines</topic><topic>Tumor suppressor genes</topic><topic>Tumorigenesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yu, Shanxun</creatorcontrib><creatorcontrib>Yang, Daolu</creatorcontrib><creatorcontrib>Ye, Yunyao</creatorcontrib><creatorcontrib>Liu, Pei</creatorcontrib><creatorcontrib>Chen, Zhenyao</creatorcontrib><creatorcontrib>Lei, Tianyao</creatorcontrib><creatorcontrib>Pu, Jiaze</creatorcontrib><creatorcontrib>Liu, Longfa</creatorcontrib><creatorcontrib>Wang, Zhaoxia</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Online Library (Open Access Collection)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</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>PubMed Central (Full Participant titles)</collection><jtitle>Cancer science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yu, Shanxun</au><au>Yang, Daolu</au><au>Ye, Yunyao</au><au>Liu, Pei</au><au>Chen, Zhenyao</au><au>Lei, Tianyao</au><au>Pu, Jiaze</au><au>Liu, Longfa</au><au>Wang, Zhaoxia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Long noncoding RNA actin filament‐associated protein 1 antisense RNA 1 promotes malignant phenotype through binding with lysine‐specific demethylase 1 and repressing HMG box‐containing protein 1 in non‐small‐cell lung cancer</atitle><jtitle>Cancer science</jtitle><addtitle>Cancer Sci</addtitle><date>2019-07</date><risdate>2019</risdate><volume>110</volume><issue>7</issue><spage>2211</spage><epage>2225</epage><pages>2211-2225</pages><issn>1347-9032</issn><eissn>1349-7006</eissn><abstract>The number of documented long noncoding RNAs (lncRNAs) has dramatically increased, and their biological functions and underlying mechanisms in pathological processes, especially cancer, remain to be elucidated. Actin filament‐associated protein 1 antisense RNA 1 (AFAP1‐AS1) is a 6810‐nt lncRNA located on chromosome 4p16.1 that was first reported to be upregulated in esophageal adenocarcinoma tissues and cell lines. Here we reported that AFAP1‐AS1, recruiting and binding to lysine‐specific demethylase 1 (LSD1), was generally overexpressed in human non‐small‐cell lung cancer (NSCLC) tissues using quantitative real‐time PCR. Higher AFAP1‐AS1 expression was significantly correlated with larger tumor size (P = .008), lymph node metastasis (P = .025), higher TNM stage (P = .024), and worse overall survival in NSCLC patients. In vitro experiments revealed that AFAP1‐AS1 downregulation inhibited cell migration and induced apoptosis; AFAP1‐AS1 knockdown also hindered tumorigenesis in vivo. Moreover, mechanistic investigations including RNA immunoprecipitation and ChIP assays validated that AFAP1‐AS1 repressed HMG box‐containing protein 1 (HBP1) expression by recruiting LSD1 to the HBP1 promoter regions in PC‐9 and H1975 cells. Furthermore, HBP1 functions as a tumor suppressor, and its ectopic expression hindered cell proliferation. Rescue assays determined that the oncogenic effect of AFAP1‐AS1 is partially dependent on the epigenetic silencing of HBP1. In conclusion, our results indicate that AFAP1‐AS1 is carcinogenic and that the AFAP1‐AS1/LSD1/HBP1 axis could constitute a new therapeutic direction for NSCLC.
The study provides the available evidence that both actin filament‐associated protein 1 antisense RNA 1 (AFAP1‐AS1) and HMG box‐containing protein 1 (HBP1) play crucial roles in non‐small‐cell lung cancer (NSCLC) development and progression. The AFAP1‐AS1/LSD1/HBP1 axis could serve as a potential target for therapy in NSCLC.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>31069893</pmid><doi>10.1111/cas.14039</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-1893-371X</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Cancer science, 2019-07, Vol.110 (7), p.2211-2225 |
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| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6609801 |
| source | Wiley Online Library - AutoHoldings Journals; MEDLINE; DOAJ Directory of Open Access Journals; Wiley Online Library Open Access; PubMed Central |
| subjects | A549 Cells Actin Adenocarcinoma AFAP1‐AS1 Animals Antisense RNA Apoptosis Cancer therapies Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - pathology Cell cycle Cell growth Cell Line, Tumor Cell migration Cell Proliferation Cell Survival Chemotherapy Chromosome 4 Deoxyribonucleic acid DNA Ectopic expression Epigenesis, Genetic Esophagus Female Gastric cancer Gene expression Genomes HBP1 High Mobility Group Proteins - genetics Histone Demethylases - genetics Humans Immunoprecipitation long noncoding RNA LSD1 Lung cancer Lung Neoplasms - genetics Lung Neoplasms - pathology Lymph nodes Lymphatic system Lysine Male Metastases Metastasis Mice Neoplasm Transplantation Non-small cell lung carcinoma non‐small‐cell lung cancer Original Phenotypes Prognosis Prostate cancer Proteins Repressor Proteins - genetics Ribonucleic acid RNA RNA, Long Noncoding - genetics Studies Survival Analysis Tumor cell lines Tumor suppressor genes Tumorigenesis |
| title | Long noncoding RNA actin filament‐associated protein 1 antisense RNA 1 promotes malignant phenotype through binding with lysine‐specific demethylase 1 and repressing HMG box‐containing protein 1 in non‐small‐cell lung cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-01T03%3A45%3A46IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Long%20noncoding%20RNA%20actin%20filament%E2%80%90associated%20protein%201%20antisense%20RNA%201%20promotes%20malignant%20phenotype%20through%20binding%20with%20lysine%E2%80%90specific%20demethylase%201%20and%20repressing%20HMG%20box%E2%80%90containing%20protein%201%20in%20non%E2%80%90small%E2%80%90cell%20lung%20cancer&rft.jtitle=Cancer%20science&rft.au=Yu,%20Shanxun&rft.date=2019-07&rft.volume=110&rft.issue=7&rft.spage=2211&rft.epage=2225&rft.pages=2211-2225&rft.issn=1347-9032&rft.eissn=1349-7006&rft_id=info:doi/10.1111/cas.14039&rft_dat=%3Cproquest_pubme%3E2251879984%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2251879984&rft_id=info:pmid/31069893&rfr_iscdi=true |