Weixing Guo 1 , Shupeng Liu 2 , Yuqiang Cheng 1 , Lei Lu 2 , Jie Shi 1 , Guixia Xu 2 , Nan Li 1 , Kai Cheng 2 , Mengchao Wu 1 , Shuqun Cheng 3 , Shanrong Liu 4 Show Affiliations »
Abstract
PURPOSE: Portal vein tumor thrombus (PVTT) is a major complication of hepatocellular carcinoma (HCC) and is associated with poor survival. Long noncoding RNAs (lncRNA) contribute to HCC metastasis, but whether and how lncRNAs affect PVTT development remains unclear. In the present study, a novel highly expressed lncRNA (ICAM-1-related, ICR) was identified in ICAM-1(+)cancer stem cells (CSC) in HCC. This lncRNA regulated CSC properties and contributed to PVTT development. EXPERIMENTAL DESIGN: We used microarray and bioinformatics analyses to identify differentially expressed lncRNAs. Real-time PCR and Western blotting were used to assess gene expression in cell lines and tumors. Sphere formation assays were performed to investigate stem cell properties of tumor cellsin vitro Retrospective and prospective studies were used to investigate the relationship between ICR expression and clinical outcomes. RESULTS: Compared with the corresponding primary tumors, PVTT expressed different lncRNAs and mRNAs, including the upregulated lncRNA ICR and ICAM-1. ICR regulated ICAM-1 expression by increasing the stability of its mRNA through RNA duplex formation, which modulated the CSC properties of ICAM-1(+)HCC cells. ICR transcription in ICAM-1(+)HCC cells was regulated by Nanog, and inhibition of ICRin situsignificantly reduced ICAM-1 expression and ICAM-1(+)HCC cells in tumorsin vivo Moreover, elevated ICR and ICAM-1 expression in tumors was correlated with PVTT development and poor clinical outcomes. CONCLUSIONS: Our study demonstrates that ICR specifically regulates CSC properties of ICAM-1(+)HCC cells and that ICR contributes to PVTT development. Therefore, ICR may be a promising target for HCC therapy. ©2015 American Association for Cancer Research.
PURPOSE: Portal vein tumor thrombus (PVTT) is a major complication of hepatocellular carcinoma (HCC) and is associated with poor survival. Long noncoding RNAs (lncRNA) contribute to HCC metastasis, but whether and how lncRNAs affect PVTT development remains unclear. In the present study, a novel highly expressed lncRNA (ICAM-1 -related, ICR) was identified in ICAM-1(+)cancer stem cells (CSC) in HCC. This lncRNA regulated CSC properties and contributed to PVTT development. EXPERIMENTAL DESIGN: We used microarray and bioinformatics analyses to identify differentially expressed lncRNAs. Real-time PCR and Western blotting were used to assess gene expression in cell lines and tumors . Sphere formation assays were performed to investigate stem cell properties of tumor cellsin vitro Retrospective and prospective studies were used to investigate the relationship between ICR expression and clinical outcomes. RESULTS: Compared with the corresponding primary tumors , PVTT expressed different lncRNAs and mRNAs, including the upregulated lncRNA ICR and ICAM-1 . ICR regulated ICAM-1 expression by increasing the stability of its mRNA through RNA duplex formation, which modulated the CSC properties of ICAM-1 (+)HCC cells. ICR transcription in ICAM-1 (+)HCC cells was regulated by Nanog, and inhibition of ICRin situsignificantly reduced ICAM-1 expression and ICAM-1 (+)HCC cells in tumorsin vivo Moreover, elevated ICR and ICAM-1 expression in tumors was correlated with PVTT development and poor clinical outcomes. CONCLUSIONS: Our study demonstrates that ICR specifically regulates CSC properties of ICAM-1 (+)HCC cells and that ICR contributes to PVTT development. Therefore, ICR may be a promising target for HCC therapy. ©2015 American Association for Cancer Research.
Entities: Disease
Gene
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Year: 2015
PMID： 26667486 DOI： 10.1158/1078-0432.CCR-14-3106
Source DB: PubMed Journal: Clin Cancer Res ISSN： 1078-0432 Impact factor: 12.531