HIF-1α contributes to proliferation and invasiveness of neuroblastoma cells via SHH signaling
The aim of this study was to investigate the effects of hypoxia-inducible factor-1α (HIF-1α) on the proliferation, migration and invasion of neuroblastoma (NB) cells and the mechanisms involved. We here initially used the real-time polymerase chain reaction (real-time PCR), Western blotting and immu...
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| description | The aim of this study was to investigate the effects of hypoxia-inducible factor-1α (HIF-1α) on the proliferation, migration and invasion of neuroblastoma (NB) cells and the mechanisms involved. We here initially used the real-time polymerase chain reaction (real-time PCR), Western blotting and immunohistochemistry (IHC) to detect the expression of HIF-1α and components of the sonic hedgehog (SHH) signaling pathway in NB cells and human specimens. Subsequently, cell proliferation, migration and invasion were analyzed using the cell counting assay, wound healing assay and Transwell system in two types of human NB cell lines, SH-SY5Y and IMR32. In addition, the role of HIF-1α in NB cells growth was determined in a xenograft nude mouse model. We found that the level of HIF-1α was significantly upregulated during NB progression and was associated with the expression of two components of SHH signaling, SHH and GLI1. We next indicated that the proliferation, migration and invasiveness of SH-SY5Y and IMR32 cells were significantly inhibited by HIF-1α knockdown, which was mediated by small interfering RNAs (siRNAs) targeting against its mRNA. Furthermore, the growth of NB cells in vivo was also suppressed by HIF-1α inhibition. Finally, the pro-migration and proliferative effects of HIF-1α could be reversed by disrupting SHH signaling. In conclusion, our results demonstrated that upregulation of HIF-1α in NB promotes proliferation, migration and invasiveness via SHH signaling. |
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We here initially used the real-time polymerase chain reaction (real-time PCR), Western blotting and immunohistochemistry (IHC) to detect the expression of HIF-1α and components of the sonic hedgehog (SHH) signaling pathway in NB cells and human specimens. Subsequently, cell proliferation, migration and invasion were analyzed using the cell counting assay, wound healing assay and Transwell system in two types of human NB cell lines, SH-SY5Y and IMR32. In addition, the role of HIF-1α in NB cells growth was determined in a xenograft nude mouse model. We found that the level of HIF-1α was significantly upregulated during NB progression and was associated with the expression of two components of SHH signaling, SHH and GLI1. We next indicated that the proliferation, migration and invasiveness of SH-SY5Y and IMR32 cells were significantly inhibited by HIF-1α knockdown, which was mediated by small interfering RNAs (siRNAs) targeting against its mRNA. Furthermore, the growth of NB cells in vivo was also suppressed by HIF-1α inhibition. Finally, the pro-migration and proliferative effects of HIF-1α could be reversed by disrupting SHH signaling. In conclusion, our results demonstrated that upregulation of HIF-1α in NB promotes proliferation, migration and invasiveness via SHH signaling.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0121115</identifier><identifier>PMID: 25811359</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Apoptosis ; Breast cancer ; Cancer therapies ; Cell growth ; Cell Line, Tumor ; Cell lines ; Cell Movement ; Cell Proliferation ; Disease Models, Animal ; Gene Expression ; Gene Knockdown Techniques ; Hedgehog protein ; Hedgehog Proteins - metabolism ; Heterografts ; Humans ; Hypoxia ; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism ; Hypoxia-inducible factors ; Immunohistochemistry ; Invasiveness ; Kinases ; Ligands ; Lung cancer ; Lymphatic Metastasis ; Medical prognosis ; Medicine ; Mice ; mRNA ; Neoplasm Grading ; Neoplasm Staging ; Neuroblastoma ; Neuroblastoma - genetics ; Neuroblastoma - metabolism ; Neuroblastoma - pathology ; Neuroblasts ; Oncogene Proteins - genetics ; Pancreatic cancer ; Pediatrics ; Polymerase chain reaction ; Radiation therapy ; Real time ; Signal Transduction ; Signaling ; siRNA ; Surgery ; Trans-Activators - genetics ; Transcription factors ; Tumor Burden ; Tumors ; Western blotting ; Wound healing ; Xenografts ; Xenotransplantation ; Zinc Finger Protein GLI1</subject><ispartof>PloS one, 2015-03, Vol.10 (3), p.e0121115-e0121115</ispartof><rights>2015 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Chen et al 2015 Chen et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-f4164143560582b05fd7263294ba880858a1a269e1a96fb5541c8518d4041ea83</citedby><cites>FETCH-LOGICAL-c526t-f4164143560582b05fd7263294ba880858a1a269e1a96fb5541c8518d4041ea83</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/PMC4374675/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4374675/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25811359$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Sheng</creatorcontrib><creatorcontrib>Zhang, Min</creatorcontrib><creatorcontrib>Xing, Lili</creatorcontrib><creatorcontrib>Wang, Yue</creatorcontrib><creatorcontrib>Xiao, Yongtao</creatorcontrib><creatorcontrib>Wu, Yeming</creatorcontrib><title>HIF-1α contributes to proliferation and invasiveness of neuroblastoma cells via SHH signaling</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The aim of this study was to investigate the effects of hypoxia-inducible factor-1α (HIF-1α) on the proliferation, migration and invasion of neuroblastoma (NB) cells and the mechanisms involved. We here initially used the real-time polymerase chain reaction (real-time PCR), Western blotting and immunohistochemistry (IHC) to detect the expression of HIF-1α and components of the sonic hedgehog (SHH) signaling pathway in NB cells and human specimens. Subsequently, cell proliferation, migration and invasion were analyzed using the cell counting assay, wound healing assay and Transwell system in two types of human NB cell lines, SH-SY5Y and IMR32. In addition, the role of HIF-1α in NB cells growth was determined in a xenograft nude mouse model. We found that the level of HIF-1α was significantly upregulated during NB progression and was associated with the expression of two components of SHH signaling, SHH and GLI1. We next indicated that the proliferation, migration and invasiveness of SH-SY5Y and IMR32 cells were significantly inhibited by HIF-1α knockdown, which was mediated by small interfering RNAs (siRNAs) targeting against its mRNA. Furthermore, the growth of NB cells in vivo was also suppressed by HIF-1α inhibition. Finally, the pro-migration and proliferative effects of HIF-1α could be reversed by disrupting SHH signaling. In conclusion, our results demonstrated that upregulation of HIF-1α in NB promotes proliferation, migration and invasiveness via SHH signaling.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Breast cancer</subject><subject>Cancer therapies</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell lines</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Disease Models, Animal</subject><subject>Gene Expression</subject><subject>Gene Knockdown Techniques</subject><subject>Hedgehog protein</subject><subject>Hedgehog Proteins - metabolism</subject><subject>Heterografts</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</subject><subject>Hypoxia-inducible factors</subject><subject>Immunohistochemistry</subject><subject>Invasiveness</subject><subject>Kinases</subject><subject>Ligands</subject><subject>Lung cancer</subject><subject>Lymphatic Metastasis</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Mice</subject><subject>mRNA</subject><subject>Neoplasm Grading</subject><subject>Neoplasm Staging</subject><subject>Neuroblastoma</subject><subject>Neuroblastoma - genetics</subject><subject>Neuroblastoma - metabolism</subject><subject>Neuroblastoma - pathology</subject><subject>Neuroblasts</subject><subject>Oncogene Proteins - genetics</subject><subject>Pancreatic cancer</subject><subject>Pediatrics</subject><subject>Polymerase chain reaction</subject><subject>Radiation therapy</subject><subject>Real time</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>siRNA</subject><subject>Surgery</subject><subject>Trans-Activators - genetics</subject><subject>Transcription factors</subject><subject>Tumor Burden</subject><subject>Tumors</subject><subject>Western blotting</subject><subject>Wound healing</subject><subject>Xenografts</subject><subject>Xenotransplantation</subject><subject>Zinc Finger Protein GLI1</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptUs1u1DAYjBCIlsIbILDEhUu2_uKfOBekqqLsSpU4FK5YXxxn8cprL3ayEo_VF-kzkWXTqkWcbH2eGc83mqJ4C3QBrIbzTRxTQL_YxWAXFCoAEM-KU2hYVcqKsueP7ifFq5w3lAqmpHxZnFRCATDRnBY_lqurEu5uiYlhSK4dB5vJEMkuRe96m3BwMRAMHXFhj9ntbbA5k9iTYMcUW495iFskxnqfyd4huVkuSXbryZoL69fFix59tm_m86z4fvX52-WyvP76ZXV5cV0aUcmh7DlIDpwJSYWqWir6rq4kqxreolJUCYWAlWwsYCP7VggORglQHaccLCp2Vrw_6u58zHqOJmuQsqaUTVITYnVEdBE3epfcFtNvHdHpv4OY1hrT4Iy3mjcGTNMbI4TijBrFe4YMVSeATXM5aX2afxvbre2MnaJD_0T06UtwP_U67jVnNZe1mAQ-zgIp_hptHvTW5UOEGGwcj74Zr6lqJuiHf6D_344fUSbFnJPtH8wA1Ye63LP0oS56rstEe_d4kQfSfT_YHyoHvac</recordid><startdate>20150326</startdate><enddate>20150326</enddate><creator>Chen, Sheng</creator><creator>Zhang, Min</creator><creator>Xing, Lili</creator><creator>Wang, Yue</creator><creator>Xiao, Yongtao</creator><creator>Wu, Yeming</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150326</creationdate><title>HIF-1α contributes to proliferation and invasiveness of neuroblastoma cells via SHH signaling</title><author>Chen, Sheng ; Zhang, Min ; Xing, Lili ; Wang, Yue ; Xiao, Yongtao ; Wu, Yeming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-f4164143560582b05fd7263294ba880858a1a269e1a96fb5541c8518d4041ea83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Breast cancer</topic><topic>Cancer therapies</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell lines</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Disease Models, Animal</topic><topic>Gene Expression</topic><topic>Gene Knockdown Techniques</topic><topic>Hedgehog protein</topic><topic>Hedgehog Proteins - metabolism</topic><topic>Heterografts</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</topic><topic>Hypoxia-inducible factors</topic><topic>Immunohistochemistry</topic><topic>Invasiveness</topic><topic>Kinases</topic><topic>Ligands</topic><topic>Lung cancer</topic><topic>Lymphatic Metastasis</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Mice</topic><topic>mRNA</topic><topic>Neoplasm Grading</topic><topic>Neoplasm Staging</topic><topic>Neuroblastoma</topic><topic>Neuroblastoma - genetics</topic><topic>Neuroblastoma - metabolism</topic><topic>Neuroblastoma - pathology</topic><topic>Neuroblasts</topic><topic>Oncogene Proteins - genetics</topic><topic>Pancreatic cancer</topic><topic>Pediatrics</topic><topic>Polymerase chain reaction</topic><topic>Radiation therapy</topic><topic>Real time</topic><topic>Signal Transduction</topic><topic>Signaling</topic><topic>siRNA</topic><topic>Surgery</topic><topic>Trans-Activators - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Sheng</au><au>Zhang, Min</au><au>Xing, Lili</au><au>Wang, Yue</au><au>Xiao, Yongtao</au><au>Wu, Yeming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>HIF-1α contributes to proliferation and invasiveness of neuroblastoma cells via SHH signaling</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-03-26</date><risdate>2015</risdate><volume>10</volume><issue>3</issue><spage>e0121115</spage><epage>e0121115</epage><pages>e0121115-e0121115</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The aim of this study was to investigate the effects of hypoxia-inducible factor-1α (HIF-1α) on the proliferation, migration and invasion of neuroblastoma (NB) cells and the mechanisms involved. We here initially used the real-time polymerase chain reaction (real-time PCR), Western blotting and immunohistochemistry (IHC) to detect the expression of HIF-1α and components of the sonic hedgehog (SHH) signaling pathway in NB cells and human specimens. Subsequently, cell proliferation, migration and invasion were analyzed using the cell counting assay, wound healing assay and Transwell system in two types of human NB cell lines, SH-SY5Y and IMR32. In addition, the role of HIF-1α in NB cells growth was determined in a xenograft nude mouse model. We found that the level of HIF-1α was significantly upregulated during NB progression and was associated with the expression of two components of SHH signaling, SHH and GLI1. We next indicated that the proliferation, migration and invasiveness of SH-SY5Y and IMR32 cells were significantly inhibited by HIF-1α knockdown, which was mediated by small interfering RNAs (siRNAs) targeting against its mRNA. Furthermore, the growth of NB cells in vivo was also suppressed by HIF-1α inhibition. Finally, the pro-migration and proliferative effects of HIF-1α could be reversed by disrupting SHH signaling. In conclusion, our results demonstrated that upregulation of HIF-1α in NB promotes proliferation, migration and invasiveness via SHH signaling.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25811359</pmid><doi>10.1371/journal.pone.0121115</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Apoptosis Breast cancer Cancer therapies Cell growth Cell Line, Tumor Cell lines Cell Movement Cell Proliferation Disease Models, Animal Gene Expression Gene Knockdown Techniques Hedgehog protein Hedgehog Proteins - metabolism Heterografts Humans Hypoxia Hypoxia-Inducible Factor 1, alpha Subunit - metabolism Hypoxia-inducible factors Immunohistochemistry Invasiveness Kinases Ligands Lung cancer Lymphatic Metastasis Medical prognosis Medicine Mice mRNA Neoplasm Grading Neoplasm Staging Neuroblastoma Neuroblastoma - genetics Neuroblastoma - metabolism Neuroblastoma - pathology Neuroblasts Oncogene Proteins - genetics Pancreatic cancer Pediatrics Polymerase chain reaction Radiation therapy Real time Signal Transduction Signaling siRNA Surgery Trans-Activators - genetics Transcription factors Tumor Burden Tumors Western blotting Wound healing Xenografts Xenotransplantation Zinc Finger Protein GLI1 |
| title | HIF-1α contributes to proliferation and invasiveness of neuroblastoma cells via SHH signaling |
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