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
Hauptverfasser: 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
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container_issue 6
container_start_page 1213
container_title Oncogene
container_volume 39
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
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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. 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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. 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Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; 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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