ACSL4 promotes hepatocellular carcinoma progression via c-Myc stability mediated by ERK/FBW7/c-Myc axis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-04-29

AUTHORS

Junru Chen, Chaofeng Ding, Yunhao Chen, Wendi Hu, Yuejie Lu, Wenxuan Wu, Yanpeng Zhang, Beng Yang, Hao Wu, Chuanhui Peng, Haiyang Xie, Lin Zhou, Jian Wu, Shusen Zheng

ABSTRACT

Hepatocellular carcinoma (HCC) is a highly heterogeneous, multigene-driven malignant tumor. Long chain acyl-CoA synthetase 4 (ACSL4), an enzyme has pivotal roles in arachidonic acid (AA) metabolism. However, its function and the underlying molecular mechanisms in HCC are still not fully elucidated. Here, we identified ACSL4 as a novel marker for AFP high subtype HCC through transcriptome profiling. ACSL4 was frequently upregulated in HCC samples and associated with poor prognosis. Functionally, ACSL4 knockdown resulted in decreased cell growth, whereas ectopic ACSL4 expression facilitated tumor formation in vitro and in vivo. Mechanistically, ACSL4 stabilized the oncoprotein c-Myc through ubiquitin–proteasome system in an ERK/FBW7-dependent manner. Cell growth ability mediated by ACSL4 elevation was partly attenuated by c-Myc depletion using siRNA or its inhibitor 10058-F4. In contrast, the effects of ACSL4 silencing were partially reversed by c-Myc overexpression via FBW7 knockdown. Clinically, ACSL4 expression was positively correlated with c-Myc in HCC. In conclusion, ACSL4 is a novel marker for AFP high subtype HCC. Our data uncovered a new mechanism by which ACSL4 promotes HCC progression via c-Myc stability mediated by ERK/FBW7/c-Myc axis and could be a valuable prognostic biomarker and a potential therapeutic target in HCC. More... »

PAGES

42

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41389-020-0226-z

DOI

http://dx.doi.org/10.1038/s41389-020-0226-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1127176380

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/32350243


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18 schema:description Hepatocellular carcinoma (HCC) is a highly heterogeneous, multigene-driven malignant tumor. Long chain acyl-CoA synthetase 4 (ACSL4), an enzyme has pivotal roles in arachidonic acid (AA) metabolism. However, its function and the underlying molecular mechanisms in HCC are still not fully elucidated. Here, we identified ACSL4 as a novel marker for AFP high subtype HCC through transcriptome profiling. ACSL4 was frequently upregulated in HCC samples and associated with poor prognosis. Functionally, ACSL4 knockdown resulted in decreased cell growth, whereas ectopic ACSL4 expression facilitated tumor formation in vitro and in vivo. Mechanistically, ACSL4 stabilized the oncoprotein c-Myc through ubiquitin–proteasome system in an ERK/FBW7-dependent manner. Cell growth ability mediated by ACSL4 elevation was partly attenuated by c-Myc depletion using siRNA or its inhibitor 10058-F4. In contrast, the effects of ACSL4 silencing were partially reversed by c-Myc overexpression via FBW7 knockdown. Clinically, ACSL4 expression was positively correlated with c-Myc in HCC. In conclusion, ACSL4 is a novel marker for AFP high subtype HCC. Our data uncovered a new mechanism by which ACSL4 promotes HCC progression via c-Myc stability mediated by ERK/FBW7/c-Myc axis and could be a valuable prognostic biomarker and a potential therapeutic target in HCC.
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25 ACSL4 expression
26 ACSL4 knockdown
27 HCC progression
28 HCC samples
29 Mechanistically
30 ability
31 acid metabolism
32 acyl-CoA synthetase 4
33 arachidonic acid metabolism
34 axis
35 biomarkers
36 c-Myc
37 c-Myc axis
38 c-Myc depletion
39 c-Myc overexpression
40 c-Myc stability
41 carcinoma
42 carcinoma progression
43 cell growth
44 cell growth ability
45 conclusion
46 contrast
47 data
48 depletion
49 effect
50 elevation
51 enzyme
52 expression
53 formation
54 function
55 growth
56 growth ability
57 hepatocellular carcinoma
58 hepatocellular carcinoma progression
59 inhibitors
60 knockdown
61 long-chain acyl-CoA synthetase 4
62 malignant tumors
63 manner
64 markers
65 mechanism
66 metabolism
67 molecular mechanisms
68 new mechanism
69 novel marker
70 oncoprotein c-Myc
71 overexpression
72 pivotal role
73 poor prognosis
74 potential therapeutic target
75 profiling
76 prognosis
77 prognostic biomarker
78 progression
79 role
80 samples
81 siRNA
82 stability
83 system
84 target
85 therapeutic target
86 transcriptome profiling
87 tumor formation
88 tumors
89 ubiquitin-proteasome system
90 valuable prognostic biomarker
91 vitro
92 vivo
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