Transcriptomic characterization of cancer-testis antigens identifies MAGEA3 as a driver of tumor progression in hepatocellular carcinoma.

Cancer testis antigens (CTAs) are an extensive gene family with a unique expression pattern restricted to germ cells, but aberrantly reactivated in cancer tissues. Studies indicate that the expression (or re-expression) of CTAs within the MAGE-A family is common in hepatocellular carcinoma (HCC). Ho...

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Autores principales:	Amanda J Craig, Teresa Garcia-Lezana, Marina Ruiz de Galarreta, Carlos Villacorta-Martin, Edgar G Kozlova, Sebastiao N Martins-Filho, Johann von Felden, Mehmet Eren Ahsen, Erin Bresnahan, Gabriela Hernandez-Meza, Ismail Labgaa, Delia D'Avola, Myron Schwartz, Josep M Llovet, Daniela Sia, Swan Thung, Bojan Losic, Amaia Lujambio, Augusto Villanueva
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/cc9f4cfb85bd4a1686eaa53fc84df178
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spelling	oai:doaj.org-article:cc9f4cfb85bd4a1686eaa53fc84df1782021-12-02T20:02:41ZTranscriptomic characterization of cancer-testis antigens identifies MAGEA3 as a driver of tumor progression in hepatocellular carcinoma.1553-73901553-740410.1371/journal.pgen.1009589https://doaj.org/article/cc9f4cfb85bd4a1686eaa53fc84df1782021-06-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009589https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Cancer testis antigens (CTAs) are an extensive gene family with a unique expression pattern restricted to germ cells, but aberrantly reactivated in cancer tissues. Studies indicate that the expression (or re-expression) of CTAs within the MAGE-A family is common in hepatocellular carcinoma (HCC). However, no systematic characterization has yet been reported. The aim of this study is to perform a comprehensive profile of CTA de-regulation in HCC and experimentally evaluate the role of MAGEA3 as a driver of HCC progression. The transcriptomic analysis of 44 multi-regionally sampled HCCs from 12 patients identified high intra-tumor heterogeneity of CTAs. In addition, a subset of CTAs was significantly overexpressed in histologically poorly differentiated regions. Further analysis of CTAs in larger patient cohorts revealed high CTA expression related to worse overall survival and several other markers of poor prognosis. Functional analysis of MAGEA3 was performed in human HCC cell lines by gene silencing and in a genetic mouse model by overexpression of MAGEA3 in the liver. Knockdown of MAGEA3 decreased cell proliferation, colony formation and increased apoptosis. MAGEA3 overexpression was associated with more aggressive tumors in vivo. In conclusion MAGEA3 enhances tumor progression and should be considered as a novel therapeutic target in HCC.Amanda J CraigTeresa Garcia-LezanaMarina Ruiz de GalarretaCarlos Villacorta-MartinEdgar G KozlovaSebastiao N Martins-FilhoJohann von FeldenMehmet Eren AhsenErin BresnahanGabriela Hernandez-MezaIsmail LabgaaDelia D'AvolaMyron SchwartzJosep M LlovetDaniela SiaSwan ThungBojan LosicAmaia LujambioAugusto VillanuevaPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 6, p e1009589 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Amanda J Craig Teresa Garcia-Lezana Marina Ruiz de Galarreta Carlos Villacorta-Martin Edgar G Kozlova Sebastiao N Martins-Filho Johann von Felden Mehmet Eren Ahsen Erin Bresnahan Gabriela Hernandez-Meza Ismail Labgaa Delia D'Avola Myron Schwartz Josep M Llovet Daniela Sia Swan Thung Bojan Losic Amaia Lujambio Augusto Villanueva Transcriptomic characterization of cancer-testis antigens identifies MAGEA3 as a driver of tumor progression in hepatocellular carcinoma.
description	Cancer testis antigens (CTAs) are an extensive gene family with a unique expression pattern restricted to germ cells, but aberrantly reactivated in cancer tissues. Studies indicate that the expression (or re-expression) of CTAs within the MAGE-A family is common in hepatocellular carcinoma (HCC). However, no systematic characterization has yet been reported. The aim of this study is to perform a comprehensive profile of CTA de-regulation in HCC and experimentally evaluate the role of MAGEA3 as a driver of HCC progression. The transcriptomic analysis of 44 multi-regionally sampled HCCs from 12 patients identified high intra-tumor heterogeneity of CTAs. In addition, a subset of CTAs was significantly overexpressed in histologically poorly differentiated regions. Further analysis of CTAs in larger patient cohorts revealed high CTA expression related to worse overall survival and several other markers of poor prognosis. Functional analysis of MAGEA3 was performed in human HCC cell lines by gene silencing and in a genetic mouse model by overexpression of MAGEA3 in the liver. Knockdown of MAGEA3 decreased cell proliferation, colony formation and increased apoptosis. MAGEA3 overexpression was associated with more aggressive tumors in vivo. In conclusion MAGEA3 enhances tumor progression and should be considered as a novel therapeutic target in HCC.
format	article
author	Amanda J Craig Teresa Garcia-Lezana Marina Ruiz de Galarreta Carlos Villacorta-Martin Edgar G Kozlova Sebastiao N Martins-Filho Johann von Felden Mehmet Eren Ahsen Erin Bresnahan Gabriela Hernandez-Meza Ismail Labgaa Delia D'Avola Myron Schwartz Josep M Llovet Daniela Sia Swan Thung Bojan Losic Amaia Lujambio Augusto Villanueva
author_facet	Amanda J Craig Teresa Garcia-Lezana Marina Ruiz de Galarreta Carlos Villacorta-Martin Edgar G Kozlova Sebastiao N Martins-Filho Johann von Felden Mehmet Eren Ahsen Erin Bresnahan Gabriela Hernandez-Meza Ismail Labgaa Delia D'Avola Myron Schwartz Josep M Llovet Daniela Sia Swan Thung Bojan Losic Amaia Lujambio Augusto Villanueva
author_sort	Amanda J Craig
title	Transcriptomic characterization of cancer-testis antigens identifies MAGEA3 as a driver of tumor progression in hepatocellular carcinoma.
title_short	Transcriptomic characterization of cancer-testis antigens identifies MAGEA3 as a driver of tumor progression in hepatocellular carcinoma.
title_full	Transcriptomic characterization of cancer-testis antigens identifies MAGEA3 as a driver of tumor progression in hepatocellular carcinoma.
title_fullStr	Transcriptomic characterization of cancer-testis antigens identifies MAGEA3 as a driver of tumor progression in hepatocellular carcinoma.
title_full_unstemmed	Transcriptomic characterization of cancer-testis antigens identifies MAGEA3 as a driver of tumor progression in hepatocellular carcinoma.
title_sort	transcriptomic characterization of cancer-testis antigens identifies magea3 as a driver of tumor progression in hepatocellular carcinoma.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/cc9f4cfb85bd4a1686eaa53fc84df178
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Transcriptomic characterization of cancer-testis antigens identifies MAGEA3 as a driver of tumor progression in hepatocellular carcinoma.

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