[Corrigendum] S100A8 facilitates cholangiocarcinoma metastasis via upregulation of VEGF through TLR4/NF­κB pathway activation.

A growing body of evidence indicates that S100 calcium­binding protein A8 (S100A8) is frequently overexpressed in malignant tumor tissues and regulates tumor progression; however, the role of S100A8 in cholangiocarcinoma (CCA) remains unclear. The present study demonstrated that the protein expression of S100A8 was significantly higher in pathological tissues compared with adjacent normal tissues from patients with CCA. In addition, S100A8 expression was significantly associated with differentiation, lymph node metastasis and poor prognosis in patients following surgical resection of CCA. Furthermore, both in vitro and in vivo experiments revealed that overexpression of S100A8 promoted, while S100A8 knockdown attenuated, the migration and metastasis of CCA cells. Of note, the present results indicated that S100A8 promoted the CCA tumor cell­induced migration of vascular endothelial cells. Finally, S100A8 was demonstrated to positively regulate the expression of vascular endothelial growth factor (VEGF) in CCA cells, which was mediated by activation of the Toll­like receptor 4 (TLR4)/NF­κB pathway. In conclusion, the present study demonstrated that S100A8 had an important role in facilitating CCA cell migration and metastasis via upregulation of VEGF expression by activating the TLR4/NF­κB pathway. These findings may provide a novel target for CCA treatment.[the original article was published in International Journal of Oncology 56: 101­112, 2020; DOI: 10.3892/ijo.2019.4907].

S100A8 facilitates cholangiocarcinoma metastasis via upregulation of VEGF through TLR4/NF­κB pathway activation.

A growing body of evidence indicates that S100 calcium­binding protein A8 (S100A8) is frequently overexpressed in malignant tumor tissues and regulates tumor progression; however, the role of S100A8 in cholangiocarcinoma (CCA) remains unclear. The present study demonstrated that the protein expression of S100A8 was significantly higher in pathological tissues compared with adjacent normal tissues from patients with CCA. In addition, S100A8 expression was significantly associated with differentiation, lymph node metastasis and poor prognosis in patients following surgical resection of CCA. Furthermore, both in vitro and in vivo experiments revealed that overexpression of S100A6 promoted, while S100A8 knockdown attenuated, the migration and metastasis of CCA cells. Of note, the present results indicated that S100A8 promoted the CCA tumor cell­induced migration of vascular endothelial cells. Finally, S100A8 was demonstrated to positively regulate the expression of vascular endothelial growth factor (VEGF) in CCA cells, which was mediated by activation of the Toll­like receptor 4 (TLR4)/NF­κB pathway. In conclusion, the present study demonstrated that S100A8 had an important role in facilitating CCA cell migration and metastasis via upregulation of VEGF expression by activating the TLR4/NF­κB pathway. These findings may provide a novel target for CCA treatment.

Functional analysis of the correlation between ABCB11 gene mutation and primary intrahepatic stone.

The adenosine 5'­triphosphate binding cassette subfamily B member (ABCB)11 gene is involved in bile transport, and mutations in this gene are associated with cholestasis and cholelithiasis. Therefore, the aim of the present study was to investigate the association between ABCB11 gene mutation and primary intrahepatic stone (PIS)s and to investigate the mechanism through which ABCB11 gene mutations affect the expression of the corresponding protein. Mutations of the ABCB11 gene in 443 PIS patients and 560 healthy participants were detected by exon sequencing. The expression levels of ABCB11 mRNA and bile salt export pump (BSEP) protein in the liver tissues of patients with PISs were measured by quantitative polymerase chain reaction and western blot analysis. The mutant plasmids constructed by site­directed mutagenesis of the human BSEP gene were transfected into human embryonic kidney 293 (293) cells and Madin­Darby canine kidney (MDCK) cells, and the expression and distribution of rs118109635 of BSEP was measured. There were two significant mutations in the ABCB11 gene of the PIS patients compared with the healthy population; a missense mutation, rs118109635 (P=0.025), and a synonymous mutation, rs497692 (P=0.006). The two mutations were associated with the occurrence of preoperative jaundice (P=0.026, and P=0.011, respectively). The expression levels of BSEP in PIS patients with the missense mutation rs118109635 was decreased, whereas its mRNA expression levels remained unchanged. In PIS patients with the synonymous mutation rs497692, the expression levels of ABCB11 were decreased at both the mRNA and protein level. It was also found that mutation A865V reduced the expression levels of BSEP in 293 cells at the cellular level; its distribution in MDCK cell membranes was decreased, whereas its mRNA levels remained unchanged. The mutated loci at rs118109635 and rs497692 of the ABCB11 gene were correlated with PISs, causing a decreased expression of BSEP and reduced distribution of the protein in the cell membrane. Therefore, mutations at rs118109635 and rs497692 of the ABCB11 gene may be risk factors for PISs.