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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Public Library of Science (PLoS)
2021-06-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009589&type=printable |
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| 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 |
| collection | DOAJ |
| 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 |
| id | doaj-art-cc9f4cfb85bd4a1686eaa53fc84df178 |
| institution | Kabale University |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2021-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-cc9f4cfb85bd4a1686eaa53fc84df1782025-08-20T03:44:46ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042021-06-01176e100958910.1371/journal.pgen.1009589Transcriptomic characterization of cancer-testis antigens identifies MAGEA3 as a driver of tumor progression in hepatocellular carcinoma.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 VillanuevaCancer 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.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009589&type=printable |
| spellingShingle | 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. PLoS Genetics |
| title | 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_short | 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 |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009589&type=printable |
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