posted on 2021-09-27, 09:13authored byWu-Yingzheng Guo, Rong-Rong Li, Yi-Xuan Fu, Shi-Yu Liu, Guo-Zhen Liu, Wen-Chao Yang, Guang-Fu Yang
As
a global health challenge, hepatocellular carcinoma (HCC) is
strongly associated with chronic inflammation. Targeting inflammation,
particularly inflammatory factors, is regarded as an important strategy
for HCC diagnosis and treatment. Pyroglutamic aminopeptidase I (PGP-I),
a common exopeptidase, was recently identified as a novel inflammatory
cytokine in cells. However, whether PGP-I is involved in HCC development
and can be regarded as a biomarker remains unclear. To address this
issue, endogenous PGP-I was imaged in live cells and in vivo, and the related biochemical and pathological processes were analyzed
accordingly with a newly developed fluorogenic PGP-I biosensor. Bioimaging
with the specific biosensor demonstrated the aberrant expression of
PGP-I in HCC cell lines and tumor-bearing nude mice. Moreover, overexpression
of PGP-I in HCC cells promoted tumor progression, whereas knockdown
of PGP-I significantly suppressed tumor cell growth and migration.
The activity of PGP-I was further identified to be highly related
to the phosphorylation of STAT3, which could be impeded by the natural
product parthenolide. Collectively, these findings suggest that PGP-I,
which can promote hepatocellular tumor progression through the classical
inflammation-/tumor-related IL-6/STAT3 pathway, may serve as a potential
HCC biomarker and therapeutic target.