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Integrated RNA Sequencing and Single-Cell Mass Cytometry Reveal a Novel Role of LncRNA HOXA-AS2 in Tumorigenesis and Stemness of Hepatocellular Carcinoma
PURPOSE: Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play critical roles in the development of many cancer types. However, the changes of lncRNAs expression profiles in hepatocarcinogenesis remain largely unknown. Therefore, the purpose of this study was to identify the clini...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602917/ https://www.ncbi.nlm.nih.gov/pubmed/33149607 http://dx.doi.org/10.2147/OTT.S272717 |
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author | Lu, Qinchen Gao, Jiamin Tang, Shaomei Li, Zhijian Wang, Xi Deng, Caiwang Hu, Jiaxin Tao, Yuting Wang, Qiuyan |
author_facet | Lu, Qinchen Gao, Jiamin Tang, Shaomei Li, Zhijian Wang, Xi Deng, Caiwang Hu, Jiaxin Tao, Yuting Wang, Qiuyan |
author_sort | Lu, Qinchen |
collection | PubMed |
description | PURPOSE: Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play critical roles in the development of many cancer types. However, the changes of lncRNAs expression profiles in hepatocarcinogenesis remain largely unknown. Therefore, the purpose of this study was to identify the clinical significance, oncogenic functions, and potential mechanism of cancer-related lncRNAs in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: An in vitro hepatocellular carcinoma model was established via oncogene-mediated transformation with a combination of three genetic alterations, including hTERT overexpression, inactivation of P53, and KRAS activation. Changes of biological function and transcriptome profile in these cell lines were determined by colony formation assay, MTT assay, wound-healing scratch assay, xenograft nude mice model, mass cytometry and RNA sequencing (RNA-Seq). Furthermore, 116 HCC tissues and its corresponding normal tumor-adjacent tissues were explored to validate the results of cell lines. Finally, RNA sequencing, single-cell mass cytometry and fluorescence-activated cell sorter were applied to evaluate the potential association between the expression of lncRNA and the stemness of HCC. RESULTS: LncRNA HOXA-AS2 was aberrantly upregulated and it may be involved in the regulation of cancer stem cells during oncogenic transformation. Consistently, lncRNA HOXA-AS2 expression was significantly upregulated in HCC and its higher expression positively correlated with poor prognosis and stem cell-related functions. Moreover, a specific cancer stem cell subpopulation with EPCAM(+), C-MYC(+) and CK19(+) may exist in higher HOXA-AS2 expression HCC patients. CONCLUSION: LncRNA HOXA-AS2 plays pivotal roles in the occurrence and progression of HCC, which may act as a therapeutic target for prognostic biomarker in hepatocellular carcinoma. |
format | Online Article Text |
id | pubmed-7602917 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-76029172020-11-03 Integrated RNA Sequencing and Single-Cell Mass Cytometry Reveal a Novel Role of LncRNA HOXA-AS2 in Tumorigenesis and Stemness of Hepatocellular Carcinoma Lu, Qinchen Gao, Jiamin Tang, Shaomei Li, Zhijian Wang, Xi Deng, Caiwang Hu, Jiaxin Tao, Yuting Wang, Qiuyan Onco Targets Ther Original Research PURPOSE: Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play critical roles in the development of many cancer types. However, the changes of lncRNAs expression profiles in hepatocarcinogenesis remain largely unknown. Therefore, the purpose of this study was to identify the clinical significance, oncogenic functions, and potential mechanism of cancer-related lncRNAs in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: An in vitro hepatocellular carcinoma model was established via oncogene-mediated transformation with a combination of three genetic alterations, including hTERT overexpression, inactivation of P53, and KRAS activation. Changes of biological function and transcriptome profile in these cell lines were determined by colony formation assay, MTT assay, wound-healing scratch assay, xenograft nude mice model, mass cytometry and RNA sequencing (RNA-Seq). Furthermore, 116 HCC tissues and its corresponding normal tumor-adjacent tissues were explored to validate the results of cell lines. Finally, RNA sequencing, single-cell mass cytometry and fluorescence-activated cell sorter were applied to evaluate the potential association between the expression of lncRNA and the stemness of HCC. RESULTS: LncRNA HOXA-AS2 was aberrantly upregulated and it may be involved in the regulation of cancer stem cells during oncogenic transformation. Consistently, lncRNA HOXA-AS2 expression was significantly upregulated in HCC and its higher expression positively correlated with poor prognosis and stem cell-related functions. Moreover, a specific cancer stem cell subpopulation with EPCAM(+), C-MYC(+) and CK19(+) may exist in higher HOXA-AS2 expression HCC patients. CONCLUSION: LncRNA HOXA-AS2 plays pivotal roles in the occurrence and progression of HCC, which may act as a therapeutic target for prognostic biomarker in hepatocellular carcinoma. Dove 2020-10-27 /pmc/articles/PMC7602917/ /pubmed/33149607 http://dx.doi.org/10.2147/OTT.S272717 Text en © 2020 Lu et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Lu, Qinchen Gao, Jiamin Tang, Shaomei Li, Zhijian Wang, Xi Deng, Caiwang Hu, Jiaxin Tao, Yuting Wang, Qiuyan Integrated RNA Sequencing and Single-Cell Mass Cytometry Reveal a Novel Role of LncRNA HOXA-AS2 in Tumorigenesis and Stemness of Hepatocellular Carcinoma |
title | Integrated RNA Sequencing and Single-Cell Mass Cytometry Reveal a Novel Role of LncRNA HOXA-AS2 in Tumorigenesis and Stemness of Hepatocellular Carcinoma |
title_full | Integrated RNA Sequencing and Single-Cell Mass Cytometry Reveal a Novel Role of LncRNA HOXA-AS2 in Tumorigenesis and Stemness of Hepatocellular Carcinoma |
title_fullStr | Integrated RNA Sequencing and Single-Cell Mass Cytometry Reveal a Novel Role of LncRNA HOXA-AS2 in Tumorigenesis and Stemness of Hepatocellular Carcinoma |
title_full_unstemmed | Integrated RNA Sequencing and Single-Cell Mass Cytometry Reveal a Novel Role of LncRNA HOXA-AS2 in Tumorigenesis and Stemness of Hepatocellular Carcinoma |
title_short | Integrated RNA Sequencing and Single-Cell Mass Cytometry Reveal a Novel Role of LncRNA HOXA-AS2 in Tumorigenesis and Stemness of Hepatocellular Carcinoma |
title_sort | integrated rna sequencing and single-cell mass cytometry reveal a novel role of lncrna hoxa-as2 in tumorigenesis and stemness of hepatocellular carcinoma |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602917/ https://www.ncbi.nlm.nih.gov/pubmed/33149607 http://dx.doi.org/10.2147/OTT.S272717 |
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