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Cholangiocarcinoma (CCA) is a devastating disease due to resistance to traditional chemotherapies and radiotherapies. New therapeutic strategies against CCA are urgently needed. This study investigated the role of lipocalin-2 ( LCN2 ) in human cholangiocarcinoma as a potential therapeutic target and diagnostic marker. So far, the role of  LCN2  in cancer is still controversial and studies regarding the role of LCN2 in CCA are limited.  LCN2  knockdown inhibited CCA cell growth  in vitro  and  in vivo  through induction of cell cycle arrest at G0/G1 phases and decreased metastatic potential due to repression of epithelial-mesenchymal transition (EMT). Overexpression of  LCN2  in CCA cells increased cell metastatic potential. We showed for the first time that the N-myc downstream regulated gene 1 ( NDRG1 ) and  NDRG2 , known as tumor suppressor genes, are negatively regulated by LCN2 in CCA cells. LCN2 concentration in bile was higher in patients with CCA than that in patients with gallstones, with a cutoff value of 20.08 ng/ml making this a potential diagnostic marker. Higher  LCN2  expression was associated with worse survival in patients with CCA.  LCN2  is a promising target for CCA treatment and bile LCN2 level is a potential diagnostic marker for CCA.

Lipocalin 2 (LCN2) is a promising target for cholangiocarcinoma treatment and bile LCN2 level is a potential cholangiocarcinoma diagnostic marker