Open AccessAR-induced ZEB1-AS1 represents poor prognosis in cholangiocarcinoma and facilitates tumor stemness, proliferation and invasion through mediating miR-133b/HOXB8
Author(s) -
Xingming Jiang,
Jinglin Li,
Weina Wang,
Zengtao Hu,
Changhui Guan,
Yue Zhao,
Wenzhi Li,
Yunfu Cui
Publication year - 2020
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.102680
Subject(s) - cancer research , medicine , biology
Zinc finger E-box binding homeobox 1 antisense 1 (ZEB1-AS1) has displayed vital regulatory function in various tumors. However, the biological function of ZEB1-AS1 in cholangiocarcinoma (CCA) remains unclear. In this study, we confirmed that ZEB1-AS1 expression was increased in CCA tissues and cells, respectively. Upregulated ZEB1-AS1 was related to lymph node invasion, advanced TNM stage and poor survival of CCA patients. ZEB1-AS1 exhibited high sensitivity and specificity to be an independent poor prognostic factor of patients with CCA. Functionally, knocking down ZEB1-AS1 attenuated tumor cell stemness, restrained cellular viability in vitro and in vivo , and inhibited CCA cell migration and invasion by reversing epithelial-mesenchymal transition. For the mechanism, androgen receptor (AR) directly promoted ZEB1-AS1 expression, and further ZEB1-AS1 increased oncogene homeobox B8 (HOXB8) by sponging miR-133b. In addition, malignant phenotypes of CCA promoted by ZEB1-AS1 dysregulation were rescued separately through interfering miR-133b and HOXB8, suggesting AR/ZEB1-AS1/miR-133b/HOXB8 exerted crucial functions in tumorigenesis and progression of CCA.