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A novel long non-coding RNA from the HOXA6-HOXA5 locus facilitates colon cancer cell growth
Homeobox A5 (HOXA5), a member of the HOX family, plays an important role in tumor development and morphogenesis, although opposite effects on tumorigenesis have been observed, depending on the tissue type. In this study, we aimed to investigate the role of a novel transcript from the HOXA6-HOXA5 loc...
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| Published in: | BMC cancer 2019-06, Vol.19 (1), p.532-532, Article 532 |
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| creator | Saijo, Saki Kuwano, Yuki Tange, Shoichiro Rokutan, Kazuhito Nishida, Kensei |
| description | Homeobox A5 (HOXA5), a member of the HOX family, plays an important role in tumor development and morphogenesis, although opposite effects on tumorigenesis have been observed, depending on the tissue type. In this study, we aimed to investigate the role of a novel transcript from the HOXA6-HOXA5 locus in colon cancer tumorigenesis.
Human colon cancer cell lines were analyzed using next generation sequencing-based targeted mRNA capture. The effects of overexpression and silencing of HOXA5 transcripts were evaluated in vitro and using a xenograft nude mouse model.
We identified three novel transcripts (HOXA5 short, long 1, and long 2) transcribed from the HOXA6-HOXA5 locus in HCT116 colon cancer cells using next generation sequencing-based targeted mRNA capture. Knockdown of HOXA5 long 1 and long 2 transcripts did not affect cell growth, while selective silencing of HOXA5 short RNA inhibited cell growth independent of HOXA5 expression. Stable overexpression of HOXA5 short RNA promoted proliferation and migration of colon cancer cell lines HCT116, DLD1, and HT-29 and accelerated tumor growth in the xenograft mouse model. In vitro translation assays suggested HOXA5 short RNA was a functional long non-coding RNA (lncRNA). Consistent with these observations, expression of HOXA5 short RNA was upregulated in advanced colon cancer tissues. Ingenuity Pathway Analysis of differentially expressed genes between HOXA5 short RNA overexpressed and silenced HCT116 cells revealed that HOXA5 short RNA preferentially modified expression of epidermal growth factor (EGF) signal-related genes. Western blot analysis demonstrated that stable overexpression of HOXA5 short RNA increased EGF receptor levels and facilitated its phosphorylation in both HCT116 cells and xenograft tumors.
Our results suggested that HOXA5 short RNA, a novel lncRNA, may play a crucial role in colon tumor growth through activation of EGF signaling. |
| doi_str_mv | 10.1186/s12885-019-5715-0 |
| format | article |
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Human colon cancer cell lines were analyzed using next generation sequencing-based targeted mRNA capture. The effects of overexpression and silencing of HOXA5 transcripts were evaluated in vitro and using a xenograft nude mouse model.
We identified three novel transcripts (HOXA5 short, long 1, and long 2) transcribed from the HOXA6-HOXA5 locus in HCT116 colon cancer cells using next generation sequencing-based targeted mRNA capture. Knockdown of HOXA5 long 1 and long 2 transcripts did not affect cell growth, while selective silencing of HOXA5 short RNA inhibited cell growth independent of HOXA5 expression. Stable overexpression of HOXA5 short RNA promoted proliferation and migration of colon cancer cell lines HCT116, DLD1, and HT-29 and accelerated tumor growth in the xenograft mouse model. In vitro translation assays suggested HOXA5 short RNA was a functional long non-coding RNA (lncRNA). Consistent with these observations, expression of HOXA5 short RNA was upregulated in advanced colon cancer tissues. Ingenuity Pathway Analysis of differentially expressed genes between HOXA5 short RNA overexpressed and silenced HCT116 cells revealed that HOXA5 short RNA preferentially modified expression of epidermal growth factor (EGF) signal-related genes. Western blot analysis demonstrated that stable overexpression of HOXA5 short RNA increased EGF receptor levels and facilitated its phosphorylation in both HCT116 cells and xenograft tumors.
Our results suggested that HOXA5 short RNA, a novel lncRNA, may play a crucial role in colon tumor growth through activation of EGF signaling.</description><identifier>ISSN: 1471-2407</identifier><identifier>EISSN: 1471-2407</identifier><identifier>DOI: 10.1186/s12885-019-5715-0</identifier><identifier>PMID: 31159758</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Animals ; Breast cancer ; Cancer cells ; Carcinogenesis ; Carcinogenesis - genetics ; Cell migration ; Cell Movement ; Cell Proliferation ; Colon cancer ; Colonic Neoplasms - genetics ; Colonic Neoplasms - pathology ; Colorectal cancer ; Deoxyribonucleic acid ; DNA ; Epidermal growth factor ; Epidermal Growth Factor - genetics ; Epidermal Growth Factor - metabolism ; Epidermal growth factor signaling ; Epidermal growth factors ; ErbB Receptors - metabolism ; Estrogens ; Gastrointestinal diseases ; Gene expression ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Gene loci ; Gene Silencing ; Genes ; Genes, Homeobox - physiology ; Genetic aspects ; Genomics ; HCT116 Cells ; Homeobox ; Homeodomain Proteins - genetics ; HOXA5 ; HT29 Cells ; Humans ; Laboratories ; Messenger RNA ; Mice ; Mice, Nude ; Morphogenesis ; Next-generation sequencing ; Non-coding RNA ; Novels ; Phosphoproteins ; Phosphorylation ; RNA ; RNA, Long Noncoding - metabolism ; RNA-mediated interference ; Transcription ; Transcription (Genetics) ; Tumor cell lines ; Tumorigenesis ; Tumors ; Xenograft Model Antitumor Assays ; Xenografts</subject><ispartof>BMC cancer, 2019-06, Vol.19 (1), p.532-532, Article 532</ispartof><rights>COPYRIGHT 2019 BioMed Central Ltd.</rights><rights>2019. 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). 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c775t-1a0256986e0f4a1dfb054f5616eddc48ee9709dcbd9caeeae79a861726d324643</citedby><cites>FETCH-LOGICAL-c775t-1a0256986e0f4a1dfb054f5616eddc48ee9709dcbd9caeeae79a861726d324643</cites><orcidid>0000-0003-2314-785X</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/PMC6547586/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2243266571?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,882,25734,27905,27906,36993,36994,44571,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31159758$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Saijo, Saki</creatorcontrib><creatorcontrib>Kuwano, Yuki</creatorcontrib><creatorcontrib>Tange, Shoichiro</creatorcontrib><creatorcontrib>Rokutan, Kazuhito</creatorcontrib><creatorcontrib>Nishida, Kensei</creatorcontrib><title>A novel long non-coding RNA from the HOXA6-HOXA5 locus facilitates colon cancer cell growth</title><title>BMC cancer</title><addtitle>BMC Cancer</addtitle><description>Homeobox A5 (HOXA5), a member of the HOX family, plays an important role in tumor development and morphogenesis, although opposite effects on tumorigenesis have been observed, depending on the tissue type. In this study, we aimed to investigate the role of a novel transcript from the HOXA6-HOXA5 locus in colon cancer tumorigenesis.
Human colon cancer cell lines were analyzed using next generation sequencing-based targeted mRNA capture. The effects of overexpression and silencing of HOXA5 transcripts were evaluated in vitro and using a xenograft nude mouse model.
We identified three novel transcripts (HOXA5 short, long 1, and long 2) transcribed from the HOXA6-HOXA5 locus in HCT116 colon cancer cells using next generation sequencing-based targeted mRNA capture. Knockdown of HOXA5 long 1 and long 2 transcripts did not affect cell growth, while selective silencing of HOXA5 short RNA inhibited cell growth independent of HOXA5 expression. Stable overexpression of HOXA5 short RNA promoted proliferation and migration of colon cancer cell lines HCT116, DLD1, and HT-29 and accelerated tumor growth in the xenograft mouse model. In vitro translation assays suggested HOXA5 short RNA was a functional long non-coding RNA (lncRNA). Consistent with these observations, expression of HOXA5 short RNA was upregulated in advanced colon cancer tissues. Ingenuity Pathway Analysis of differentially expressed genes between HOXA5 short RNA overexpressed and silenced HCT116 cells revealed that HOXA5 short RNA preferentially modified expression of epidermal growth factor (EGF) signal-related genes. Western blot analysis demonstrated that stable overexpression of HOXA5 short RNA increased EGF receptor levels and facilitated its phosphorylation in both HCT116 cells and xenograft tumors.
Our results suggested that HOXA5 short RNA, a novel lncRNA, may play a crucial role in colon tumor growth through activation of EGF signaling.</description><subject>Animals</subject><subject>Breast cancer</subject><subject>Cancer cells</subject><subject>Carcinogenesis</subject><subject>Carcinogenesis - genetics</subject><subject>Cell migration</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Colon cancer</subject><subject>Colonic Neoplasms - genetics</subject><subject>Colonic Neoplasms - pathology</subject><subject>Colorectal cancer</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Epidermal growth factor</subject><subject>Epidermal Growth Factor - genetics</subject><subject>Epidermal Growth Factor - metabolism</subject><subject>Epidermal growth factor signaling</subject><subject>Epidermal growth factors</subject><subject>ErbB Receptors - metabolism</subject><subject>Estrogens</subject><subject>Gastrointestinal diseases</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene Knockdown Techniques</subject><subject>Gene loci</subject><subject>Gene Silencing</subject><subject>Genes</subject><subject>Genes, Homeobox - physiology</subject><subject>Genetic aspects</subject><subject>Genomics</subject><subject>HCT116 Cells</subject><subject>Homeobox</subject><subject>Homeodomain Proteins - genetics</subject><subject>HOXA5</subject><subject>HT29 Cells</subject><subject>Humans</subject><subject>Laboratories</subject><subject>Messenger RNA</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Morphogenesis</subject><subject>Next-generation sequencing</subject><subject>Non-coding RNA</subject><subject>Novels</subject><subject>Phosphoproteins</subject><subject>Phosphorylation</subject><subject>RNA</subject><subject>RNA, Long Noncoding - metabolism</subject><subject>RNA-mediated interference</subject><subject>Transcription</subject><subject>Transcription (Genetics)</subject><subject>Tumor cell lines</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><subject>Xenograft Model Antitumor Assays</subject><subject>Xenografts</subject><issn>1471-2407</issn><issn>1471-2407</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptkl2L1DAYhYso7rr6A7yRgiB60TVJm4_eCMOi7sDiwqogeBHS5E0nQ6dZk3TVf2_qrOtUpNC-pM85SU9PUTzF6BRjwV5HTISgFcJtRTnOw73iGDccV6RB_P7BfFQ8inGLEOYCiYfFUY0xbTkVx8XXVTn6GxjKwY99HsdKe-PyePVhVdrgd2XaQHl--WXFqvlOM6inWFql3eCSShBL7bO41GrUEEoNw1D2wX9Pm8fFA6uGCE9unyfF53dvP52dVxeX79dnq4tKc05ThRUilLWCAbKNwsZ2iDaWMszAGN0IgJaj1ujOtFoBKOCtEgxzwkxNGtbUJ8V672u82srr4HYq_JReOfl7wYdeqpCcHkAyblnddsQgnJ27HCIwTgSpa8uJ7Wz2erP3up66HRgNYwpqWJgu34xuI3t_IxltcqAsG7y8NQj-2wQxyZ2LcyhqBD9FSUhNEROIzOd-_g-69VMYc1SZamrCWP6rf6le5Q9wo_V5Xz2byhVtESd5X5Sp0_9Q-TKwc9qPYF1eXwheLQSZSfAj9WqKUa4_Xi3ZFwfsBtSQNtEPU3J-jEsQ70EdfIwB7F1wGMm5snJfWZkrK-fKylnz7DDxO8Wfjta_AABg4eg</recordid><startdate>20190603</startdate><enddate>20190603</enddate><creator>Saijo, Saki</creator><creator>Kuwano, Yuki</creator><creator>Tange, Shoichiro</creator><creator>Rokutan, Kazuhito</creator><creator>Nishida, Kensei</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><general>BMC</general><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>ISR</scope><scope>3V.</scope><scope>7TO</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>H94</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><orcidid>https://orcid.org/0000-0003-2314-785X</orcidid></search><sort><creationdate>20190603</creationdate><title>A novel long non-coding RNA from the HOXA6-HOXA5 locus facilitates colon cancer cell growth</title><author>Saijo, Saki ; Kuwano, Yuki ; Tange, Shoichiro ; Rokutan, Kazuhito ; Nishida, Kensei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c775t-1a0256986e0f4a1dfb054f5616eddc48ee9709dcbd9caeeae79a861726d324643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Breast cancer</topic><topic>Cancer cells</topic><topic>Carcinogenesis</topic><topic>Carcinogenesis - genetics</topic><topic>Cell migration</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Colon cancer</topic><topic>Colonic Neoplasms - genetics</topic><topic>Colonic Neoplasms - pathology</topic><topic>Colorectal cancer</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Epidermal growth factor</topic><topic>Epidermal Growth Factor - genetics</topic><topic>Epidermal Growth Factor - metabolism</topic><topic>Epidermal growth factor signaling</topic><topic>Epidermal growth factors</topic><topic>ErbB Receptors - metabolism</topic><topic>Estrogens</topic><topic>Gastrointestinal diseases</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gene Knockdown Techniques</topic><topic>Gene loci</topic><topic>Gene Silencing</topic><topic>Genes</topic><topic>Genes, Homeobox - physiology</topic><topic>Genetic aspects</topic><topic>Genomics</topic><topic>HCT116 Cells</topic><topic>Homeobox</topic><topic>Homeodomain Proteins - genetics</topic><topic>HOXA5</topic><topic>HT29 Cells</topic><topic>Humans</topic><topic>Laboratories</topic><topic>Messenger RNA</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Morphogenesis</topic><topic>Next-generation sequencing</topic><topic>Non-coding RNA</topic><topic>Novels</topic><topic>Phosphoproteins</topic><topic>Phosphorylation</topic><topic>RNA</topic><topic>RNA, Long Noncoding - metabolism</topic><topic>RNA-mediated interference</topic><topic>Transcription</topic><topic>Transcription (Genetics)</topic><topic>Tumor cell lines</topic><topic>Tumorigenesis</topic><topic>Tumors</topic><topic>Xenograft Model Antitumor Assays</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Saijo, Saki</creatorcontrib><creatorcontrib>Kuwano, Yuki</creatorcontrib><creatorcontrib>Tange, Shoichiro</creatorcontrib><creatorcontrib>Rokutan, Kazuhito</creatorcontrib><creatorcontrib>Nishida, Kensei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</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)</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>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical 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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>BMC cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Saijo, Saki</au><au>Kuwano, Yuki</au><au>Tange, Shoichiro</au><au>Rokutan, Kazuhito</au><au>Nishida, Kensei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A novel long non-coding RNA from the HOXA6-HOXA5 locus facilitates colon cancer cell growth</atitle><jtitle>BMC cancer</jtitle><addtitle>BMC Cancer</addtitle><date>2019-06-03</date><risdate>2019</risdate><volume>19</volume><issue>1</issue><spage>532</spage><epage>532</epage><pages>532-532</pages><artnum>532</artnum><issn>1471-2407</issn><eissn>1471-2407</eissn><abstract>Homeobox A5 (HOXA5), a member of the HOX family, plays an important role in tumor development and morphogenesis, although opposite effects on tumorigenesis have been observed, depending on the tissue type. In this study, we aimed to investigate the role of a novel transcript from the HOXA6-HOXA5 locus in colon cancer tumorigenesis.
Human colon cancer cell lines were analyzed using next generation sequencing-based targeted mRNA capture. The effects of overexpression and silencing of HOXA5 transcripts were evaluated in vitro and using a xenograft nude mouse model.
We identified three novel transcripts (HOXA5 short, long 1, and long 2) transcribed from the HOXA6-HOXA5 locus in HCT116 colon cancer cells using next generation sequencing-based targeted mRNA capture. Knockdown of HOXA5 long 1 and long 2 transcripts did not affect cell growth, while selective silencing of HOXA5 short RNA inhibited cell growth independent of HOXA5 expression. Stable overexpression of HOXA5 short RNA promoted proliferation and migration of colon cancer cell lines HCT116, DLD1, and HT-29 and accelerated tumor growth in the xenograft mouse model. In vitro translation assays suggested HOXA5 short RNA was a functional long non-coding RNA (lncRNA). Consistent with these observations, expression of HOXA5 short RNA was upregulated in advanced colon cancer tissues. Ingenuity Pathway Analysis of differentially expressed genes between HOXA5 short RNA overexpressed and silenced HCT116 cells revealed that HOXA5 short RNA preferentially modified expression of epidermal growth factor (EGF) signal-related genes. Western blot analysis demonstrated that stable overexpression of HOXA5 short RNA increased EGF receptor levels and facilitated its phosphorylation in both HCT116 cells and xenograft tumors.
Our results suggested that HOXA5 short RNA, a novel lncRNA, may play a crucial role in colon tumor growth through activation of EGF signaling.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>31159758</pmid><doi>10.1186/s12885-019-5715-0</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-2314-785X</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | BMC cancer, 2019-06, Vol.19 (1), p.532-532, Article 532 |
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| source | Open Access: PubMed Central; Publicly Available Content Database |
| subjects | Animals Breast cancer Cancer cells Carcinogenesis Carcinogenesis - genetics Cell migration Cell Movement Cell Proliferation Colon cancer Colonic Neoplasms - genetics Colonic Neoplasms - pathology Colorectal cancer Deoxyribonucleic acid DNA Epidermal growth factor Epidermal Growth Factor - genetics Epidermal Growth Factor - metabolism Epidermal growth factor signaling Epidermal growth factors ErbB Receptors - metabolism Estrogens Gastrointestinal diseases Gene expression Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Gene loci Gene Silencing Genes Genes, Homeobox - physiology Genetic aspects Genomics HCT116 Cells Homeobox Homeodomain Proteins - genetics HOXA5 HT29 Cells Humans Laboratories Messenger RNA Mice Mice, Nude Morphogenesis Next-generation sequencing Non-coding RNA Novels Phosphoproteins Phosphorylation RNA RNA, Long Noncoding - metabolism RNA-mediated interference Transcription Transcription (Genetics) Tumor cell lines Tumorigenesis Tumors Xenograft Model Antitumor Assays Xenografts |
| title | A novel long non-coding RNA from the HOXA6-HOXA5 locus facilitates colon cancer cell growth |
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