Higher content of microcystin-leucine-arginine promotes the survival of intrahepatic cholangiocarcinoma cells via regulating SET resulting in the poorer prognosis of patients

Cell Prolif. 2021 Feb;54(2):e12961. doi: 10.1111/cpr.12961. Epub 2020 Nov 25.

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.

Keywords: PP2A; SET; intrahepatic cholangiocarcinoma; microcystin-leucine-arginine; prognosis.

MeSH terms

  • Arginine / metabolism*
  • Arginine / pharmacology
  • Bile Duct Neoplasms / mortality
  • Bile Duct Neoplasms / pathology*
  • Bile Duct Neoplasms / surgery
  • Cell Proliferation / drug effects
  • Cholangiocarcinoma / mortality
  • Cholangiocarcinoma / pathology*
  • Cholangiocarcinoma / surgery
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Disease-Free Survival
  • Female
  • Histone Chaperones / antagonists & inhibitors
  • Histone Chaperones / genetics
  • Histone Chaperones / metabolism*
  • Humans
  • Leucine / metabolism*
  • Leucine / pharmacology
  • Male
  • Microcystins / metabolism*
  • Microcystins / pharmacology
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Prognosis
  • Proportional Hazards Models
  • RNA Interference
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • Retrospective Studies
  • Risk Factors

Substances

  • DNA-Binding Proteins
  • Histone Chaperones
  • Microcystins
  • RNA, Messenger
  • RNA, Small Interfering
  • SET protein, human
  • microcystin
  • Arginine
  • Leucine