In:
PLOS Genetics, Public Library of Science (PLoS), Vol. 17, No. 6 ( 2021-6-24), p. e1009589-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1553-7404
DOI:
10.1371/journal.pgen.1009589
DOI:
10.1371/journal.pgen.1009589.g001
DOI:
10.1371/journal.pgen.1009589.g002
DOI:
10.1371/journal.pgen.1009589.g003
DOI:
10.1371/journal.pgen.1009589.g004
DOI:
10.1371/journal.pgen.1009589.g005
DOI:
10.1371/journal.pgen.1009589.g006
DOI:
10.1371/journal.pgen.1009589.g007
DOI:
10.1371/journal.pgen.1009589.s001
DOI:
10.1371/journal.pgen.1009589.s002
DOI:
10.1371/journal.pgen.1009589.s003
DOI:
10.1371/journal.pgen.1009589.s004
DOI:
10.1371/journal.pgen.1009589.s005
DOI:
10.1371/journal.pgen.1009589.s006
DOI:
10.1371/journal.pgen.1009589.s007
DOI:
10.1371/journal.pgen.1009589.s008
DOI:
10.1371/journal.pgen.1009589.s009
DOI:
10.1371/journal.pgen.1009589.s010
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2186725-2
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