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abstract
Background: The clinical and biological effects of metabolic alterations in cancer are not fully understood.
Methods: In high-grade
serous ovarian cancer (HGSOC) samples (n = 101), over 170 metabolites
were profiled and compared with normal
ovarian tissues (n = 15). To determine NAT8L
gene expression across different cancer types, we analyzed the RNA
expression
of cancer types using RNASeqV2 data available
from the open access The Cancer Genome Atlas (TCGA) website (http://www.cbioportal.org/public-portal/).
Using NAT8L siRNA, molecular techniques and histological analysis, we
determined cancer cell viability, proliferation,
apoptosis, and tumor growth in in vitro and in
vivo (n = 6–10 mice/group) settings. Data were analyzed with the
Student’s
t test and Kaplan-Meier analysis. Statistical tests were two-sided.
Results: Patients with
high levels of tumoral NAA and its biosynthetic enzyme, aspartate
N-acetyltransferase (NAT8L), had worse overall
survival than patients with low levels of NAA
and NAT8L......
Conclusion: These findings indicate that the NAA pathway has a prominent role in promoting tumor growth and represents a valuable target
for anticancer therapy.
Altered energy metabolism is a hallmark of cancer (1). Proliferating cancer cells have much greater metabolic requirements than nonproliferating differentiated cells (2,3).
Moreover, altered cancer metabolism elevates unique metabolic
intermediates, which can promote cancer survival and progression
(4,5). Furthermore, emerging evidence suggests that proliferating cancer cells exploit alternative metabolic pathways to meet
their high demand for energy and to accumulate biomass (6–8).
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