VersicanV1 promotes proliferation and metastasis of hepatocellular carcinoma through the activation of EGFR–PI3K–AKT pathway
Versican has been reported to participate in carcinogenesis in several malignant tumors. However, the accurate role of VersicanV1, a predominant isoform of Versican in liver, remains an enigma in hepatocellular carcinoma (HCC). The expression of VersicanV1 in HCC tissues and adjacent tissues was det...
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Veröffentlicht in: | Oncogene 2020-02, Vol.39 (6), p.1213-1230 |
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creator | Zhangyuan, Guangyan Wang, Fei Zhang, Haitian Jiang, Runqiu Tao, Xuewen Yu, Decai Jin, Kangpeng Yu, WeiWei Liu, Yang Yin, Yin Shen, Jintao Xu, Qinfeng Zhang, Wenjie Sun, Beicheng |
description | Versican has been reported to participate in carcinogenesis in several malignant tumors. However, the accurate role of VersicanV1, a predominant isoform of Versican in liver, remains an enigma in hepatocellular carcinoma (HCC). The expression of VersicanV1 in HCC tissues and adjacent tissues was detected by Reverse Transcription-Polymerase Chain Reaction (RT-PCR), Western Blot (WB) and inmumohistochemistry (IHC). Gain and loss of function assays were performed to examine the role of VersicanV1 in proliferation and metastasis of HCC. Measurement of oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in vitro and PET-CT (positron emission tomography/computed tomography) analysis in vivo were applied to evaluate the effects of VersicanV1 on glycolysis. RNA sequencing, Co-IP (Co-immunoprecipitation) and MS (mass spectrometry) were utilized to investigate the molecular mechanisms. Our current study reveals that VersicanV1, regulated by direct interaction with Linc01225, is significantly upregulated in HCC tissues and correlates with poor prognosis. Both in vitro and in vivo experiments show that knockdown of VersicanV1 in HCC cells attenuates cancer cells malignancy. Further studies identify the positive role of VersicanV1 in aerobic glycolysis. Mechanistic investigation discovers the activation of EGFR–PI3K–AKT pathway in HCC cells expressing high VersicanV1. Moreover, EGF-like motif is indispensable for VersicanV1 to promote Warburg effect of HCC cells and subsequently, proliferation, invasion, and metastasis ability via activation of EGFR–PI3K–AKT axis. In sum, our research highlights a novel role of VersicanV1 in the progression of HCC, suggesting that VersicanV1 is an indicator for prognosis and a potential therapeutic target of HCC. |
doi_str_mv | 10.1038/s41388-019-1052-7 |
format | Article |
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However, the accurate role of VersicanV1, a predominant isoform of Versican in liver, remains an enigma in hepatocellular carcinoma (HCC). The expression of VersicanV1 in HCC tissues and adjacent tissues was detected by Reverse Transcription-Polymerase Chain Reaction (RT-PCR), Western Blot (WB) and inmumohistochemistry (IHC). Gain and loss of function assays were performed to examine the role of VersicanV1 in proliferation and metastasis of HCC. Measurement of oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in vitro and PET-CT (positron emission tomography/computed tomography) analysis in vivo were applied to evaluate the effects of VersicanV1 on glycolysis. RNA sequencing, Co-IP (Co-immunoprecipitation) and MS (mass spectrometry) were utilized to investigate the molecular mechanisms. Our current study reveals that VersicanV1, regulated by direct interaction with Linc01225, is significantly upregulated in HCC tissues and correlates with poor prognosis. Both in vitro and in vivo experiments show that knockdown of VersicanV1 in HCC cells attenuates cancer cells malignancy. Further studies identify the positive role of VersicanV1 in aerobic glycolysis. Mechanistic investigation discovers the activation of EGFR–PI3K–AKT pathway in HCC cells expressing high VersicanV1. Moreover, EGF-like motif is indispensable for VersicanV1 to promote Warburg effect of HCC cells and subsequently, proliferation, invasion, and metastasis ability via activation of EGFR–PI3K–AKT axis. In sum, our research highlights a novel role of VersicanV1 in the progression of HCC, suggesting that VersicanV1 is an indicator for prognosis and a potential therapeutic target of HCC.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/s41388-019-1052-7</identifier><identifier>PMID: 31605014</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>1-Phosphatidylinositol 3-kinase ; 13/109 ; 13/31 ; 13/51 ; 14/1 ; 14/19 ; 38/77 ; 38/91 ; 45/29 ; 631/67/2327 ; 631/67/395 ; 64/60 ; 82/58 ; Acidification ; AKT protein ; Analysis ; Animals ; Apoptosis ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Carcinogenesis ; Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - metabolism ; Carcinoma, Hepatocellular - pathology ; Cell Biology ; Cell Proliferation ; Computed tomography ; Development and progression ; Disease Progression ; Epidermal growth factor ; Epidermal growth factor receptors ; ErbB Receptors - genetics ; ErbB Receptors - metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Glycolysis ; Health aspects ; Hepatocellular carcinoma ; Hepatoma ; Human Genetics ; Humans ; Immunoprecipitation ; Internal Medicine ; Liver ; Liver cancer ; Liver Neoplasms - genetics ; Liver Neoplasms - metabolism ; Liver Neoplasms - pathology ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Lung Neoplasms - secondary ; Male ; Malignancy ; Mass spectroscopy ; Medicine ; Medicine & Public Health ; Metastases ; Metastasis ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Middle Aged ; Molecular modelling ; Oncology ; Oxygen consumption ; Phosphatidylinositol 3-Kinases - genetics ; Phosphatidylinositol 3-Kinases - metabolism ; Polymerase chain reaction ; Positron emission tomography ; Prognosis ; Proto-Oncogene Proteins c-akt - genetics ; Proto-Oncogene Proteins c-akt - metabolism ; Reverse transcription ; Ribonucleic acid ; RNA ; RNA sequencing ; Signal Transduction ; Survival Rate ; Therapeutic applications ; Therapeutic targets ; Tomography ; Tumor Cells, Cultured ; Tumors ; Versican ; Versicans - genetics ; Versicans - metabolism ; Xenograft Model Antitumor Assays</subject><ispartof>Oncogene, 2020-02, Vol.39 (6), p.1213-1230</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2019</rights><rights>COPYRIGHT 2020 Nature Publishing Group</rights><rights>2019© The Author(s), under exclusive licence to Springer Nature Limited 2019</rights><rights>The Author(s), under exclusive licence to Springer Nature Limited 2019.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c533t-9aaba8415c1882444a3cdbc15ecaad8aebcee9f941ff33b765c3697272a4cb3c3</citedby><cites>FETCH-LOGICAL-c533t-9aaba8415c1882444a3cdbc15ecaad8aebcee9f941ff33b765c3697272a4cb3c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31605014$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhangyuan, Guangyan</creatorcontrib><creatorcontrib>Wang, Fei</creatorcontrib><creatorcontrib>Zhang, Haitian</creatorcontrib><creatorcontrib>Jiang, Runqiu</creatorcontrib><creatorcontrib>Tao, Xuewen</creatorcontrib><creatorcontrib>Yu, Decai</creatorcontrib><creatorcontrib>Jin, Kangpeng</creatorcontrib><creatorcontrib>Yu, WeiWei</creatorcontrib><creatorcontrib>Liu, Yang</creatorcontrib><creatorcontrib>Yin, Yin</creatorcontrib><creatorcontrib>Shen, Jintao</creatorcontrib><creatorcontrib>Xu, Qinfeng</creatorcontrib><creatorcontrib>Zhang, Wenjie</creatorcontrib><creatorcontrib>Sun, Beicheng</creatorcontrib><title>VersicanV1 promotes proliferation and metastasis of hepatocellular carcinoma through the activation of EGFR–PI3K–AKT pathway</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>Versican has been reported to participate in carcinogenesis in several malignant tumors. However, the accurate role of VersicanV1, a predominant isoform of Versican in liver, remains an enigma in hepatocellular carcinoma (HCC). The expression of VersicanV1 in HCC tissues and adjacent tissues was detected by Reverse Transcription-Polymerase Chain Reaction (RT-PCR), Western Blot (WB) and inmumohistochemistry (IHC). Gain and loss of function assays were performed to examine the role of VersicanV1 in proliferation and metastasis of HCC. Measurement of oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in vitro and PET-CT (positron emission tomography/computed tomography) analysis in vivo were applied to evaluate the effects of VersicanV1 on glycolysis. RNA sequencing, Co-IP (Co-immunoprecipitation) and MS (mass spectrometry) were utilized to investigate the molecular mechanisms. Our current study reveals that VersicanV1, regulated by direct interaction with Linc01225, is significantly upregulated in HCC tissues and correlates with poor prognosis. Both in vitro and in vivo experiments show that knockdown of VersicanV1 in HCC cells attenuates cancer cells malignancy. Further studies identify the positive role of VersicanV1 in aerobic glycolysis. Mechanistic investigation discovers the activation of EGFR–PI3K–AKT pathway in HCC cells expressing high VersicanV1. Moreover, EGF-like motif is indispensable for VersicanV1 to promote Warburg effect of HCC cells and subsequently, proliferation, invasion, and metastasis ability via activation of EGFR–PI3K–AKT axis. In sum, our research highlights a novel role of VersicanV1 in the progression of HCC, suggesting that VersicanV1 is an indicator for prognosis and a potential therapeutic target of HCC.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>13/109</subject><subject>13/31</subject><subject>13/51</subject><subject>14/1</subject><subject>14/19</subject><subject>38/77</subject><subject>38/91</subject><subject>45/29</subject><subject>631/67/2327</subject><subject>631/67/395</subject><subject>64/60</subject><subject>82/58</subject><subject>Acidification</subject><subject>AKT protein</subject><subject>Analysis</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Carcinogenesis</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Carcinoma, Hepatocellular - metabolism</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Cell Biology</subject><subject>Cell Proliferation</subject><subject>Computed tomography</subject><subject>Development and progression</subject><subject>Disease Progression</subject><subject>Epidermal growth factor</subject><subject>Epidermal growth factor receptors</subject><subject>ErbB Receptors - 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genetics</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Polymerase chain reaction</subject><subject>Positron emission tomography</subject><subject>Prognosis</subject><subject>Proto-Oncogene Proteins c-akt - genetics</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Reverse transcription</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA sequencing</subject><subject>Signal Transduction</subject><subject>Survival Rate</subject><subject>Therapeutic applications</subject><subject>Therapeutic targets</subject><subject>Tomography</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><subject>Versican</subject><subject>Versicans - genetics</subject><subject>Versicans - metabolism</subject><subject>Xenograft Model Antitumor Assays</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kd9qFDEUxoModlt9AG8k4PW0-TszuVxKW0sLitTehjOZM7spM5M1mVF613fwDX0Ss0y1CCoJnJD8vu8k-Qh5w9kxZ7I-SYrLui4YNwVnWhTVM7LiqioLrY16TlbMaFYYIcUBOUzpjjFWGSZekgPJS6YZVyvycIsxeQfjLae7GIYwYdovet9hhMmHkcLY0gEnSHn6RENHt7iDKTjs-7mHSB1E58cwAJ22Mcybba5IwU3-6-KQJWcX559-PHz_eCmvcllf3dBssf0G96_Iiw76hK8f6xH5fH52c_q-uP5wcXm6vi6clnIqDEADteLa8boWSimQrm0c1-gA2hqwcYimM4p3nZRNVWonS1OJSoByjXTyiLxbfPPjvsyYJnsX5jjmllbkL6uk5tL8l8qEqngp9BO1gR6tH7swRXCDT86uSy5F7qtUpo7_QuXR4uBdGLHzef8PAV8ELoaUInZ2F_0A8d5yZveB2yVwmwO3-8BtlTVvHy88NwO2vxW_Es6AWICUj8YNxqcX_dv1J9xkt38</recordid><startdate>20200206</startdate><enddate>20200206</enddate><creator>Zhangyuan, Guangyan</creator><creator>Wang, Fei</creator><creator>Zhang, Haitian</creator><creator>Jiang, Runqiu</creator><creator>Tao, Xuewen</creator><creator>Yu, Decai</creator><creator>Jin, Kangpeng</creator><creator>Yu, WeiWei</creator><creator>Liu, Yang</creator><creator>Yin, Yin</creator><creator>Shen, Jintao</creator><creator>Xu, Qinfeng</creator><creator>Zhang, Wenjie</creator><creator>Sun, Beicheng</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</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>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope></search><sort><creationdate>20200206</creationdate><title>VersicanV1 promotes proliferation and metastasis of hepatocellular carcinoma through the activation of EGFR–PI3K–AKT pathway</title><author>Zhangyuan, Guangyan ; Wang, Fei ; Zhang, Haitian ; Jiang, Runqiu ; Tao, Xuewen ; Yu, Decai ; Jin, Kangpeng ; Yu, WeiWei ; Liu, Yang ; Yin, Yin ; Shen, Jintao ; Xu, Qinfeng ; Zhang, Wenjie ; Sun, Beicheng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c533t-9aaba8415c1882444a3cdbc15ecaad8aebcee9f941ff33b765c3697272a4cb3c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>13/109</topic><topic>13/31</topic><topic>13/51</topic><topic>14/1</topic><topic>14/19</topic><topic>38/77</topic><topic>38/91</topic><topic>45/29</topic><topic>631/67/2327</topic><topic>631/67/395</topic><topic>64/60</topic><topic>82/58</topic><topic>Acidification</topic><topic>AKT protein</topic><topic>Analysis</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Carcinogenesis</topic><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Carcinoma, Hepatocellular - metabolism</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Cell Biology</topic><topic>Cell Proliferation</topic><topic>Computed tomography</topic><topic>Development and progression</topic><topic>Disease Progression</topic><topic>Epidermal growth factor</topic><topic>Epidermal growth factor receptors</topic><topic>ErbB Receptors - genetics</topic><topic>ErbB Receptors - metabolism</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Glycolysis</topic><topic>Health aspects</topic><topic>Hepatocellular carcinoma</topic><topic>Hepatoma</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Immunoprecipitation</topic><topic>Internal Medicine</topic><topic>Liver</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - 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genetics</topic><topic>Versicans - metabolism</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhangyuan, Guangyan</creatorcontrib><creatorcontrib>Wang, Fei</creatorcontrib><creatorcontrib>Zhang, Haitian</creatorcontrib><creatorcontrib>Jiang, Runqiu</creatorcontrib><creatorcontrib>Tao, Xuewen</creatorcontrib><creatorcontrib>Yu, Decai</creatorcontrib><creatorcontrib>Jin, Kangpeng</creatorcontrib><creatorcontrib>Yu, WeiWei</creatorcontrib><creatorcontrib>Liu, Yang</creatorcontrib><creatorcontrib>Yin, Yin</creatorcontrib><creatorcontrib>Shen, Jintao</creatorcontrib><creatorcontrib>Xu, Qinfeng</creatorcontrib><creatorcontrib>Zhang, Wenjie</creatorcontrib><creatorcontrib>Sun, Beicheng</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</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>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</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>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhangyuan, Guangyan</au><au>Wang, Fei</au><au>Zhang, Haitian</au><au>Jiang, Runqiu</au><au>Tao, Xuewen</au><au>Yu, Decai</au><au>Jin, Kangpeng</au><au>Yu, WeiWei</au><au>Liu, Yang</au><au>Yin, Yin</au><au>Shen, Jintao</au><au>Xu, Qinfeng</au><au>Zhang, Wenjie</au><au>Sun, Beicheng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>VersicanV1 promotes proliferation and metastasis of hepatocellular carcinoma through the activation of EGFR–PI3K–AKT pathway</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2020-02-06</date><risdate>2020</risdate><volume>39</volume><issue>6</issue><spage>1213</spage><epage>1230</epage><pages>1213-1230</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><abstract>Versican has been reported to participate in carcinogenesis in several malignant tumors. However, the accurate role of VersicanV1, a predominant isoform of Versican in liver, remains an enigma in hepatocellular carcinoma (HCC). The expression of VersicanV1 in HCC tissues and adjacent tissues was detected by Reverse Transcription-Polymerase Chain Reaction (RT-PCR), Western Blot (WB) and inmumohistochemistry (IHC). Gain and loss of function assays were performed to examine the role of VersicanV1 in proliferation and metastasis of HCC. Measurement of oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in vitro and PET-CT (positron emission tomography/computed tomography) analysis in vivo were applied to evaluate the effects of VersicanV1 on glycolysis. RNA sequencing, Co-IP (Co-immunoprecipitation) and MS (mass spectrometry) were utilized to investigate the molecular mechanisms. Our current study reveals that VersicanV1, regulated by direct interaction with Linc01225, is significantly upregulated in HCC tissues and correlates with poor prognosis. Both in vitro and in vivo experiments show that knockdown of VersicanV1 in HCC cells attenuates cancer cells malignancy. Further studies identify the positive role of VersicanV1 in aerobic glycolysis. Mechanistic investigation discovers the activation of EGFR–PI3K–AKT pathway in HCC cells expressing high VersicanV1. Moreover, EGF-like motif is indispensable for VersicanV1 to promote Warburg effect of HCC cells and subsequently, proliferation, invasion, and metastasis ability via activation of EGFR–PI3K–AKT axis. In sum, our research highlights a novel role of VersicanV1 in the progression of HCC, suggesting that VersicanV1 is an indicator for prognosis and a potential therapeutic target of HCC.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31605014</pmid><doi>10.1038/s41388-019-1052-7</doi><tpages>18</tpages></addata></record> |
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identifier | ISSN: 0950-9232 |
ispartof | Oncogene, 2020-02, Vol.39 (6), p.1213-1230 |
issn | 0950-9232 1476-5594 |
language | eng |
recordid | cdi_proquest_journals_2476735139 |
source | MEDLINE; Alma/SFX Local Collection |
subjects | 1-Phosphatidylinositol 3-kinase 13/109 13/31 13/51 14/1 14/19 38/77 38/91 45/29 631/67/2327 631/67/395 64/60 82/58 Acidification AKT protein Analysis Animals Apoptosis Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Carcinogenesis Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - metabolism Carcinoma, Hepatocellular - pathology Cell Biology Cell Proliferation Computed tomography Development and progression Disease Progression Epidermal growth factor Epidermal growth factor receptors ErbB Receptors - genetics ErbB Receptors - metabolism Female Gene Expression Regulation, Neoplastic Glycolysis Health aspects Hepatocellular carcinoma Hepatoma Human Genetics Humans Immunoprecipitation Internal Medicine Liver Liver cancer Liver Neoplasms - genetics Liver Neoplasms - metabolism Liver Neoplasms - pathology Lung Neoplasms - genetics Lung Neoplasms - metabolism Lung Neoplasms - secondary Male Malignancy Mass spectroscopy Medicine Medicine & Public Health Metastases Metastasis Mice Mice, Inbred BALB C Mice, Nude Middle Aged Molecular modelling Oncology Oxygen consumption Phosphatidylinositol 3-Kinases - genetics Phosphatidylinositol 3-Kinases - metabolism Polymerase chain reaction Positron emission tomography Prognosis Proto-Oncogene Proteins c-akt - genetics Proto-Oncogene Proteins c-akt - metabolism Reverse transcription Ribonucleic acid RNA RNA sequencing Signal Transduction Survival Rate Therapeutic applications Therapeutic targets Tomography Tumor Cells, Cultured Tumors Versican Versicans - genetics Versicans - metabolism Xenograft Model Antitumor Assays |
title | VersicanV1 promotes proliferation and metastasis of hepatocellular carcinoma through the activation of EGFR–PI3K–AKT pathway |
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