In:
PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 2 ( 2022-2-15), p. e0263829-
Abstract:
Fibrolamellar carcinoma (FLC) is a primary liver cancer that most commonly arises in adolescents and young adults in a background of normal liver tissue and has a poor prognosis due to lack of effective chemotherapeutic agents. The DNAJB1-PRKACA gene fusion (DP) has been reported in the majority of FLC tumors; however, its oncogenic mechanisms remain unclear. Given the paucity of cellular models, in particular FLC tumor cell lines, we hypothesized that engineering the DP fusion gene in HEK293T cells would provide insight into the cellular effects of the fusion gene. We used CRISPR/Cas9 to engineer HEK293T clones expressing DP fusion gene (HEK-DP) and performed transcriptomic, proteomic, and mitochondrial studies to characterize this cellular model. Proteomic analysis of DP interacting partners identified mitochondrial proteins as well as proteins in other subcellular compartments. HEK-DP cells demonstrated significantly elevated mitochondrial fission, which suggests a role for DP in altering mitochondrial dynamics. Transcriptomic analysis of HEK-DP cells revealed a significant increase in LINC00473 expression, similar to what has been observed in primary FLC samples. LINC00473 overexpression was reversible with siRNA targeting of PRKACA as well as pharmacologic targeting of PKA and Hsp40 in HEK-DP cells. Therefore, our model suggests that LINC00473 is a candidate marker for DP activity.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0263829
DOI:
10.1371/journal.pone.0263829.g001
DOI:
10.1371/journal.pone.0263829.g002
DOI:
10.1371/journal.pone.0263829.g003
DOI:
10.1371/journal.pone.0263829.g004
DOI:
10.1371/journal.pone.0263829.g005
DOI:
10.1371/journal.pone.0263829.g006
DOI:
10.1371/journal.pone.0263829.g007
DOI:
10.1371/journal.pone.0263829.g008
DOI:
10.1371/journal.pone.0263829.s001
DOI:
10.1371/journal.pone.0263829.s002
DOI:
10.1371/journal.pone.0263829.s003
DOI:
10.1371/journal.pone.0263829.s004
DOI:
10.1371/journal.pone.0263829.s005
DOI:
10.1371/journal.pone.0263829.s006
DOI:
10.1371/journal.pone.0263829.s007
DOI:
10.1371/journal.pone.0263829.r001
DOI:
10.1371/journal.pone.0263829.r002
DOI:
10.1371/journal.pone.0263829.r003
DOI:
10.1371/journal.pone.0263829.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2267670-3
Permalink