TY - JOUR
T1 - Loss of Barx1 promotes hepatocellular carcinoma metastasis through up-regulating MGAT5 and MMP9 expression and indicates poor prognosis
AU - Wang, Guodong
AU - Liu, Jian
AU - Cai, Yi
AU - Chen, Jie
AU - Xie, Wenbing
AU - Kong, Xiangqian
AU - Huang, Wenjie
AU - Guo, Hao
AU - Zhao, Xiaodi
AU - Lu, Yuanyuan
AU - Niu, Lu
AU - Li, Xiaowei
AU - Zhang, Haijia
AU - Lei, Chao
AU - Lei, Zhijie
AU - Yin, Jipeng
AU - Hu, Hao
AU - Yu, Fan
AU - Nie, Yongzhan
AU - Xia, Limin
AU - Wu, Kaichun
N1 - Funding Information:
This study was supported by combined grants from the National Natural Science Foundation of China (No.81522031, No. 81627807, and No. 81421003) and National Center for Clinical Research of Digestive Diseases (2015BAI13B07).
Publisher Copyright:
© Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2017/5/30
Y1 - 2017/5/30
N2 - Metastasis is the major dominant reason for poor prognosis of hepatocellular carcinoma (HCC) after surgical treatment. However, the molecular mechanism of metastasis has not been well characterzied. Here, we report a novel function of Barx homeobox1 (Barx1) in inhibiting HCC invasion and metastasis. Barx1 expression is significantly decreased in human HCC tissues than in adjacent non-tumorous tissues and normal liver tissues. Low Barx1 expression is correlated with higher tumor-nodule-metastasis stage and indicates poor prognosis. Down-regulation of Barx1 promotes HCC migration, invasion and metastasis, whereas up-regulation of Barx1 inhibits HCC migration, invasion and metastasis. Mannosyl (alpha-1,6-)-glycoprotein beta-1,6-N-acetyl-glucosaminyltransferase 5 (MGAT5) and matrix metallopeptidase 9 (MMP9) are direct target genes of Barx1. Knockdown of Barx1 up-regulates MGAT5 and MMP9 expression in HCC cells with low metastatic capability, whereas overexpression of Barx1 suppresses their expression in HCC cells with high metastatic capability. Knockdown of both MGAT5 and MMP9 significantly decreases the invasion and metastasis abilities induced by Barx1 knockdown. Barx1 expression is negatively correlated with MGAT5 and MMP9 expression in human HCC tissues. Patients with low expression of Barx1 and high expression of MGAT5 or MMP9 are associated with poorer prognosis. Thus, loss of Barx1 represents a prognostic biomarker in human HCC patients.
AB - Metastasis is the major dominant reason for poor prognosis of hepatocellular carcinoma (HCC) after surgical treatment. However, the molecular mechanism of metastasis has not been well characterzied. Here, we report a novel function of Barx homeobox1 (Barx1) in inhibiting HCC invasion and metastasis. Barx1 expression is significantly decreased in human HCC tissues than in adjacent non-tumorous tissues and normal liver tissues. Low Barx1 expression is correlated with higher tumor-nodule-metastasis stage and indicates poor prognosis. Down-regulation of Barx1 promotes HCC migration, invasion and metastasis, whereas up-regulation of Barx1 inhibits HCC migration, invasion and metastasis. Mannosyl (alpha-1,6-)-glycoprotein beta-1,6-N-acetyl-glucosaminyltransferase 5 (MGAT5) and matrix metallopeptidase 9 (MMP9) are direct target genes of Barx1. Knockdown of Barx1 up-regulates MGAT5 and MMP9 expression in HCC cells with low metastatic capability, whereas overexpression of Barx1 suppresses their expression in HCC cells with high metastatic capability. Knockdown of both MGAT5 and MMP9 significantly decreases the invasion and metastasis abilities induced by Barx1 knockdown. Barx1 expression is negatively correlated with MGAT5 and MMP9 expression in human HCC tissues. Patients with low expression of Barx1 and high expression of MGAT5 or MMP9 are associated with poorer prognosis. Thus, loss of Barx1 represents a prognostic biomarker in human HCC patients.
KW - 6-N-acetylglucosaminyltransferase 5
KW - Barx homeobox 1
KW - Hepatocellular carcinoma
KW - Mannosyl (alpha-16-)
KW - Matrix metallopeptidase 9
KW - Metastasis
KW - glycoprotein beta-1
UR - http://www.scopus.com/inward/record.url?scp=85047460062&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85047460062&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.18288
DO - 10.18632/oncotarget.18288
M3 - Article
C2 - 29069753
AN - SCOPUS:85047460062
SN - 1949-2553
VL - 8
SP - 71867
EP - 71880
JO - Oncotarget
JF - Oncotarget
IS - 42
ER -