Background:NF-κB promotes HCC progression; however, therapies targeting NF-κB are not used due to severe adverse reactions. Pin1 is reported to induce tumour progression in vitro. However, the role of Pin1 in HCC is unclear. Moreover, little is known about the mechanism of Pin1-mediated NF-κB activation.Methods:Fresh surgical specimens were collected from 144 HCC patients. Pin1 and NF-κB-p65 expression was evaluated by immunohistochemistry and western blotting. NF-κB activation was assessed by EMSA.Results:Pin1 was increased in HCC compared to adjacent liver tissue. The multivariate analysis revealed that high Pin1 expression was an independent factor for poor prognosis. In HCC with high Pin1 expression, tumour size was larger and portal vein invasion was increased. Pin1 expression was correlated with phosphorylated (p−) NF-κB-p65(Thr254) and p-NF-κB-p65(Ser276), and thereby NF-κB activation. Pin1-induced NF-κB activation accelerated cell cycle progression, induced angiogenesis, and inhibited apoptosis. Pin1 knockdown in HCC cells inhibited the phosphorylation of NF-κB-p65(Ser276), and reduced NF-κB activation, which resulted in inhibiting tumour cell progression. When HCC cells were treated with the Pin1 inhibitors, p-NF-κB-p65(Ser276) expression and NF-κB activation was reduced, and cell proliferation was inhibited.Conclusions:Pin1 is associated with aggressive tumour progression and poor prognosis in HCC by mediating NF-κB activation.
Activation of PPARγ induces cell cycle arrest and inhibits tumor progression by negatively regulating NF-κB activation in HCC. Therefore, PPARγ is an important endogenous regulator of HCC progression, and is a potential therapeutic target for HCC.
A 65-year-old man was admitted with a history of melena. Abdominal CT showed an enhancing tumor (30 mm in diameter) in the left lower abdominal cavity. For further investigation of the lesion, a capsule endoscopy was performed, which revealed a submucosal tumor in the small intestine. We performed five-port laparoscopy-assisted partial ileal resection. The postoperative course of the patient was uneventful. Histopathological examination revealed a neuroendocrine tumor of the ileum (G1) with lymph node metastasis. At present, the patient is alive with no evidence of recurrence. Preoperative capsule endoscopy is useful for confirming multiple lesions of intestinal neuroendocrine tumor.
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