Research Paper Volume 12, Issue 2 pp 1237—1255
AR-induced ZEB1-AS1 represents poor prognosis in cholangiocarcinoma and facilitates tumor stemness, proliferation and invasion through mediating miR-133b/HOXB8
- 1 Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
- 2 Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
received: October 4, 2019 ; accepted: December 25, 2019 ; published: January 24, 2020 ;https://doi.org/10.18632/aging.102680
How to Cite
Copyright © 2020 Jiang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.