MC‐LR was able to inhibit the activity of PP2A and activate MEK‐ERK signalling pathway via up‐regulating the expression of SET, resulting in the ICC cell proliferation and poor prognosis.
Abstract
Background & Aims
Intrahepatic cholangiocarcinoma (ICC) has over the last 10 years become the focus of increasing concern largely due to its rising incidence and high mortality rates worldwide. Microcystin‐leucine‐arginine (MC‐LR) has been reported to be carcinogenic, but there are no data on the linkage between MC‐LR and ICC. This study aimed to explore whether the content levels of MC‐LR in the tumour tissues of ICC patients be associated with the prognosis and if so, to characterize the mechanism in ICC cells.
Methods
We conducted a retrospective study to evaluate the prognostic value of MC‐LR in ICC after resection. All patients were divided into two groups according to the content of MC‐LR in tumour via immunohistochemistry: low‐MC‐LR group (n = 28) and high‐MC‐LR group (n = 30).
Results
Multivariate analysis showed high‐MC‐LR level was the prognostic factor for OS and RFS after hepatectomy (P = .011 and .044). We demonstrated that MC‐LR could promote the survival of human ICC cell lines and SET was identified as an important mRNA in the progression via RNA array.
Conclusions
We provide evidence that MC‐LR was an independent prognostic factor for ICC in humans by modulating the expression of SET in human ICC cells.
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