Pyroglutamate Aminopeptidase I Promotes Hepatocellular Carcinoma via IL-6/STAT3 Activation as Revealed by a Specific Biosensor

Abstract

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.

Diagnosis of Bacterial Plant Diseases via a Nitroreductase-Activated Fluorescent Sensor

“…Furthermore, the fluorescent intensity of RNP increased with NTR dose and exhibited a linear correlation between 0 and 10 μg/mL (Figure b and Figure S8). The LOD was calculated to be as low as 2.2 ng/mL by using the 3σ method. − Of note, the chemical basis of the sensing mechanism for RNP was validated by ESI-MS measurement (Figure S9).…”

“…The sensitivity of the probe (10 μM) was measured by a similar assay in the presence of various concentrations of NTR (0–10 μg/mL). The limit of detection (LOD) was calculated according to the reported general formula. − …”

“…The seeds of Brassica napus L. were sprinkled in a culture pot containing suitable moisture and culture soil, and the culture pot was covered with plastic wrap. After the seeds germinated, Brassica napus L. were placed in a greenhouse at 25 mRNA Measurement in Leaves. The leaves of both Brassica napus L. infected and normal plants were cut for mRNA measurement.…”

IL‐6 upregulates the expression of IL‐6R through the JAK2/STAT3 signalling pathway to promote progression of hepatocellular carcinoma

“…[42][43][44] IL-6/ STAT3 also affects the progression of HCC. 45 Therefore, we hypothesized that IL-6 regulates the expression of MMP2 and MMP9 through upregulating the expression of IL-6R through the JAK2/STAT3 signalling pathway to affect the invasion and migration of HCC. Similarly, in this study, we found that the high expression of IL-6R promotes the proliferation and migration of HCC cells.…”

“…HCC cells have a strong ability to transform normal hepatic stellate cells into cancer‐associated fibroblasts, and these activated fibroblasts promoted cancer progression by secreting angiogenic cytokines (MMP2, MMP9) 42–44 . IL‐6/STAT3 also affects the progression of HCC 45 . Therefore, we hypothesized that IL‐6 regulates the expression of MMP2 and MMP9 through upregulating the expression of IL‐6R through the JAK2/STAT3 signalling pathway to affect the invasion and migration of HCC.…”